------------------------------------------------------------- This message has been scanned by Postini anti-virus software. =0D ------_=_NextPart_001_01C5B942.E0E82DA5-- From owner-chemistry@ccl.net Wed Sep 14 13:17:59 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29148-050914131547-17480-2NbaQmdzjXHCm+8GjNpz2w-#-server.ccl.net> X-Original-From: Alessandro Contini Content-transfer-encoding: 8BIT Content-type: text/plain; charset=ISO-8859-15 Date: Wed, 14 Sep 2005 19:15:34 +0200 MIME-version: 1.0 Sent to CCL by: Alessandro Contini [alessandro.contini-#-unimi.it] Hi, I saw the potential of the Hanessian's software CHYRON and I found it quite impressive. I think that it could be a good solution for your question. Regards Alessandro Contini Il giorno mer, 14/09/2005 alle 10.12 -0400, CCL ha scritto: > Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] > Dear CCLers: > > I need some advice about the drug discovery/design. Using structure based design, one could develope several potential small molecular inhibitors/drugs for a given protein target. Many of these compounds may appear very attractive as they satisfy all lipinski's rules and your requirements for selectivity/specificity and may even have desirable solubility/ADME profiles. These days its possible to incorporate all these features right at the computational design stage. However, the organic synthesis of the compound still remains a bottleneck as it turns out that many of the designed compounds are 'hard' to synthesize or may require many steps of synthesis. I was wondering if there are some simple guidelines in the form of literature or 'hands on' experience available which could tell the computational/medicinal chemist whether a designed compound would be easy or hard to synthesize before he/she talks to the organic chemist. > > All your responses are greatly appreciated. > > Yours sincerely > Sandeep Kumar, Ph.D. > Johns Hopkins University, > Dept. of Biology, > 106 Mudd Hall, > 3400 N. Charles St. > Baltimore, MD 21218. > Phone: 410-516-8433 > Email: kumarsan-#-jhu.edu> > > -- Alessandro Contini, Ph.D. Istituto di Chimica Organica "Alessandro Marchesini" Università degli Studi di Milano, Facoltà di Farmacia Via Venezian, 21 20133 Milano Tel. +390250314480 Fax. +390250314476 e-mail alessandro.contini-#-unimi.it From owner-chemistry@ccl.net Wed Sep 14 13:31:05 2005 From: "CCL" To: CCL Subject: CCL: double vs. split valence basis sets Message-Id: <-29150-050914132726-3095-2NbaQmdzjXHCm+8GjNpz2w*|*server.ccl.net> X-Original-From: Joslyn Y Kravitz Content-Type: TEXT/PLAIN; charset=US-ASCII; format=flowed Date: Wed, 14 Sep 2005 12:49:19 -0400 (EDT) MIME-Version: 1.0 Sent to CCL by: Joslyn Y Kravitz [jyudenfr*|*umich.edu] Hello all, I have a question of semantics that I would appreciate opinions on. I have frequently seen the 6-31G* type basis sets referred to as double-zeta basis sets. Technically, they are not double zeta basis sets, but rather are split-valence basis sets because they don't use two basis functions for the core orbitals. Am I splitting hairs here or is it actually important that the distinction is made? Thanks, Joslyn Kravitz From owner-chemistry@ccl.net Wed Sep 14 13:44:14 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29151-050914112552-8391-2NbaQmdzjXHCm+8GjNpz2w=-=server.ccl.net> X-Original-From: "Phil Hultin" Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset="us-ascii" Date: Wed, 14 Sep 2005 09:40:53 -0500 MIME-Version: 1.0 Sent to CCL by: "Phil Hultin" [hultin=-=cc.umanitoba.ca] This question about the synthetic feasibility of a computationally-selected drug candidate is a very good one, but unfortunately there is not a nice simple answer. To decide whether a structure is synthetically accessible, the only way that I can think of is to actually know organic chemistry. It is usually pretty straightforward to identify things that are "hard" to make based on relatively elementary knowledge of reactions. It is NOT straightforward to decide whether something is "easy" to make, however - at least not for molecules of any complexity. I would suggest that any computational drug designer should consider a refresher course in organic chemistry, followed by a basic introduction to the design of organic syntheses such as Stuart Warren's book "Organic Synthesis: the disconnection approach". In a computation, we generally believe that things are deterministic and thus that a single result (within round-off error) should be obtained from a fixed starting point. In synthesis, there is no single answer to the question of how to synthesize a given target. Moreover, the number of permutations grows exponentially (at least) as the size of the target grows. Thus, there is a qualitative element to determining whether something is feasible or not. Of course, I am quite aware that there is a qualitative and creative element to computational chemistry too and I do not mean to put down computational people in any way, or to set organickers up on a pedestal. Dr. Philip G. Hultin Associate Professor of Chemistry, University of Manitoba Winnipeg, MB R3T 2N2 hultin=-=cc.umanitoba.ca http://umanitoba.ca/chemistry/people/hultin -----Original Message----- > From: owner-chemistry=-=ccl.net [mailto:owner-chemistry=-=ccl.net] Sent: September 14, 2005 9:10 AM To: Hultin, Philip G. Subject: CCL: W:Computational drug design blues Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] Dear CCLers: I need some advice about the drug discovery/design. Using structure based design, one could develope several potential small molecular inhibitors/drugs for a given protein target. Many of these compounds may appear very attractive as they satisfy all lipinski's rules and your requirements for selectivity/specificity and may even have desirable solubility/ADME profiles. These days its possible to incorporate all these features right at the computational design stage. However, the organic synthesis of the compound still remains a bottleneck as it turns out that many of the designed compounds are 'hard' to synthesize or may require many steps of synthesis. I was wondering if there are some simple guidelines in the form of literature or 'hands on' experience available which could tell the computational/medicinal chemist whether a designed compound would be easy or hard to synthesize before he/she talks to the organic chemist. All your responses are greatly appreciated. Yours sincerely Sandeep Kumar, Ph.D. Johns Hopkins University, Dept. of Biology, 106 Mudd Hall, 3400 N. Charles St. Baltimore, MD 21218. Phone: 410-516-8433 Email: kumarsan=-=jhu.edu From owner-chemistry@ccl.net Wed Sep 14 13:49:55 2005 From: "CCL" To: CCL Subject: CCL: W:Y zeolite coordinates needed Message-Id: <-29152-050914130454-16323-2NbaQmdzjXHCm+8GjNpz2w!A!server.ccl.net> X-Original-From: "Jos Walkimar Carneiro" Sent to CCL by: "Jos Walkimar Carneiro" [walk!A!vm.uff.br] Does anybody has the cartesian coordinates of the T20 model of faujasite (Y) zeolite? Thank you Walkimar Carneiro From owner-chemistry@ccl.net Wed Sep 14 14:49:05 2005 From: "CCL" To: CCL Subject: CCL: Any open-source software for generation of common chemical file format Message-Id: <-29155-050914120854-19882-2NbaQmdzjXHCm+8GjNpz2w-#-server.ccl.net> X-Original-From: "Gunda Tamás" Content-Transfer-Encoding: 7bit Content-Type: text/plain; format=flowed; charset="iso-8859-1"; reply-type=original Date: Wed, 14 Sep 2005 17:25:31 +0200 MIME-Version: 1.0 Sent to CCL by: "Gunda Tamás" [tgunda2005-#-puma.unideb.hu] Lei, Mol2Mol is also capable to make batch conversions. It is a shareware program, anyway. Have a look at http://web.interware.hu/frenzy/mol2mol Tamas Gunda >> >> Sent to CCL by: "Lei Huang" [hxbus!^!yahoo.com] >> Dear CCLers: >> >> I need to convert some short peptide >> sequences(hundreds of them) into one of the common >> used chemical file formats (SDF,SMILES etc.) and >> then use them in JOELib or CDK. I know it can be >> done in some commerical packages. However, is there >> any open source software out there that can perform >> the same task in a batch manner? I'd appreciate if >> you could give some clues. >> >> Lei Huang >> M/C 563 >> University of Illinois at Chicago >> Chicago, IL 60612 >> Email: hxbus AT yahoo DOT com >> >> From owner-chemistry@ccl.net Wed Sep 14 14:49:06 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29154-050914121150-20037-2NbaQmdzjXHCm+8GjNpz2w-#-server.ccl.net> X-Original-From: "Srinivasan Parthiban" Content-Transfer-Encoding: 8bit Content-Type: text/plain;charset=iso-8859-1 Date: Wed, 14 Sep 2005 19:11:37 +0400 (RET) MIME-Version: 1.0 Sent to CCL by: "Srinivasan Parthiban" [parthiban-#-gvkbio.com] There must be few programs available on estimating the Synthetic feasibility Index. I have used it few years back using Tripos software. It is purely an empirical method where the calculation is based on the number of rings and the functional groups present in the molecule and so on. - Parthi ----------------------------------- Srinivasan Parthiban Director-Informatics GVKBIO Vukan Towers #81 Tirumalai Pillai Road T. Nagar, Chennai 600 017 INDIA Ph: +91-44-5212 5522/3399 www.gvkbio.com ---------------------------------- > > Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] > Dear CCLers: > > I need some advice about the drug discovery/design. Using structure based > design, one could develope several potential small molecular > inhibitors/drugs for a given protein target. Many of these compounds may > appear very attractive as they satisfy all lipinski's rules and your > requirements for selectivity/specificity and may even have desirable > solubility/ADME profiles. These days its possible to incorporate all these > features right at the computational design stage. However, the organic > synthesis of the compound still remains a bottleneck as it turns out that > many of the designed compounds are 'hard' to synthesize or may require > many steps of synthesis. I was wondering if there are some simple > guidelines in the form of literature or 'hands on' experience available > which could tell the computational/medicinal chemist whether a designed > compound would be easy or hard to synthesize before he/she talks to the > organic chemist. > > All your responses are greatly appreciated. > > Yours sincerely > Sandeep Kumar, Ph.D. > Johns Hopkins University, > Dept. of Biology, > 106 Mudd Hall, > 3400 N. Charles St. > Baltimore, MD 21218. > Phone: 410-516-8433 > Email: kumarsan-#-jhu.edu> To send e-mail to subscribers of CCL put the string CCL: on your Subject: > line> > Send your subscription/unsubscription requests to: > CHEMISTRY-REQUEST-#-ccl.net> > > > ----------------------------------- Srinivasan Parthiban Director-Informatics GVKBIO Vukan Towers #81 Tirumalai Pillai Road T. Nagar, Chennai 600 017 INDIA Ph: +91-44-5212 5522/3399 www.gvkbio.com ---------------------------------- From owner-chemistry@ccl.net Wed Sep 14 14:49:06 2005 From: "CCL" To: CCL Subject: CCL: W:Calculation of displacements in vibrational normal modes with MOPAC Message-Id: <-29153-050914123231-30186-2NbaQmdzjXHCm+8GjNpz2w.@.server.ccl.net> X-Original-From: "Michael Schmuker" Sent to CCL by: "Michael Schmuker" [schmuker...@...chemie.uni-frankfurt.de] Dear List, having only fundamental knowledge in quantum chemistry, I'm a bit lost on this one: I want to calculate vibrational normal modes of small organic molecules using MOPAC and the respective atom displacements for each of them. So far, I use MOPAC with the FORCE keyword, which gives me the frequencies of the vibrations and two matrices, the "Normal Coordinate Analysis" and the "Mass-Weighted Coordinate Analysis". Can anyone tell me how to get from there to the atom displacements (in x,y,z coordinates) for each vibrational mode? How can I calculate something like the example below from those matrices? Frequency 1234.5 Atom1 0.002 0.012 -0.090 Atom2 -0.123 0.087 0.089 Frequency 3548.5 Atom1 0.004 0.003 0.020 Atom2 0.003 -0.014 0.089 ... Many thanks in advance! Kind Regards, Michael Michael Schmuker Beilstein Endowed Chair of Cheminformatics University of Frankfurt schmuker AT chemie uni-frankfurt de From owner-chemistry@ccl.net Wed Sep 14 16:08:28 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29156-050914160340-10408-2NbaQmdzjXHCm+8GjNpz2w.@.server.ccl.net> X-Original-From: Eugen Leitl Content-Disposition: inline Content-Type: text/plain; charset=us-ascii Date: Wed, 14 Sep 2005 21:06:45 +0200 Mime-Version: 1.0 Sent to CCL by: Eugen Leitl [eugen...@...leitl.org] On Wed, Sep 14, 2005 at 09:40:53AM -0500, CCL wrote: > > Sent to CCL by: "Phil Hultin" [hultin=-=cc.umanitoba.ca] > This question about the synthetic feasibility of a computationally-selected > drug candidate is a very good one, but unfortunately there is not a nice > simple answer. While not a substitute for organical synthesis database between one's own two ears, a variation on the candidate queried on supplier's catalogues, empirical reaction/structure databases like CAS or Spresi http://spresi.com/ (full disclaimer: operated by my employers) and/or a synthetic reaction planner will give a hint of how difficult a target in reaction space you're trying to reach. In drug discovery, a good diversity library is one already present in the commercial catalogues, or at most one or a couple of synthetic steps remote in structure space. -- Eugen* Leitl leitl ______________________________________________________________ ICBM: 48.07100, 11.36820 http://www.leitl.org 8B29F6BE: 099D 78BA 2FD3 B014 B08A 7779 75B0 2443 8B29 F6BE From owner-chemistry@ccl.net Wed Sep 14 16:30:41 2005 From: "CCL" To: CCL Subject: CCL: double vs. split valence basis sets Message-Id: <-29157-050914155028-9430-2NbaQmdzjXHCm+8GjNpz2w|-|server.ccl.net> X-Original-From: "Shobe, David" content-class: urn:content-classes:message Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset="iso-8859-1" Date: Wed, 14 Sep 2005 15:48:25 -0400 MIME-Version: 1.0 Sent to CCL by: "Shobe, David" [dshobe|-|sud-chemieinc.com] > Am I splitting hairs here or ... No, you're doubling hairs. ;-) Usually when the "zeta" value is mentioned, it is zeta for the valence AO's. There may be times when it is necessary to make the distinction, but you can easily say the basis is double-zeta in the core AO's and triple-zeta in the valence AO's. --David Shobe, Ph.D., M.L.S. Süd-Chemie, Inc. phone (502) 634-7409 fax (502) 634-7724 Don't bother flaming me: I'm behind a firewall. -----Original Message----- > From: owner-chemistry|-|ccl.net [mailto:owner-chemistry|-|ccl.net] Sent: Wednesday, September 14, 2005 12:49 PM To: Shobe, David Subject: CCL: double vs. split valence basis sets Sent to CCL by: Joslyn Y Kravitz [jyudenfr*|*umich.edu] Hello all, I have a question of semantics that I would appreciate opinions on. I have frequently seen the 6-31G* type basis sets referred to as double-zeta basis sets. Technically, they are not double zeta basis sets, but rather are split-valence basis sets because they don't use two basis functions for the core orbitals. Am I splitting hairs here or is it actually important that the distinction is made? Thanks, Joslyn Kravitz From owner-chemistry@ccl.net Wed Sep 14 16:30:41 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29158-050914154212-8740-2NbaQmdzjXHCm+8GjNpz2w]"[server.ccl.net> X-Original-From: Gary Breton Content-transfer-encoding: 7bit Content-type: text/plain; charset="US-ASCII" Date: Wed, 14 Sep 2005 14:44:28 -0400 Mime-version: 1.0 Sent to CCL by: Gary Breton [gbreton]"[berry.edu] Speaking as an organic chemist I can tell you that the answer to your question is probably no. There is no easy way to tell whether a given compound is easy or difficult to synthesize other than to give it to a medicinal or organic chemist that has experience in and knows synthesis. For example, a compound with a nitro group at one position may be very easy to synthesize, but move it over one carbon and suddenly you have a very difficult system to synthesize. Any "simple" guidelines would probably not differentiate between the difficulty in synthesis of these types of isomers. While there have been attempts at generating software to aid in "deconstructing" molecules towards the goal of making planned syntheses easier, none of these (at least to my knowledge) is particular robust. I have never heard of an organic chemist...or seen cited in a paper...the use of such software to aid in a synthetic route. While there may be exceptions, it certainly isn't the norm. ...and I don't say all this just for the sake of job security ;) Gary W. Breton Associate Professor Hard-Working Organic Chemist Department of Chemistry Berry College PO Box 495016 Mount Berry, GA 30149 > Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] > Dear CCLers: > > I need some advice about the drug discovery/design. Using structure based > design, one could develope several potential small molecular inhibitors/drugs > for a given protein target. Many of these compounds may appear very attractive > as they satisfy all lipinski's rules and your requirements for > selectivity/specificity and may even have desirable solubility/ADME profiles. > These days its possible to incorporate all these features right at the > computational design stage. However, the organic synthesis of the compound > still remains a bottleneck as it turns out that many of the designed compounds > are 'hard' to synthesize or may require many steps of synthesis. I was > wondering if there are some simple guidelines in the form of literature or > 'hands on' experience available which could tell the computational/medicinal > chemist whether a designed compound would be easy or hard to synthesize before > he/she talks to the organic chemist. > > All your responses are greatly appreciated. > > Yours sincerely > Sandeep Kumar, Ph.D. > Johns Hopkins University, > Dept. of Biology, > 106 Mudd Hall, > 3400 N. Charles St. > Baltimore, MD 21218. > Phone: 410-516-8433 > Email: kumarsan]"[jhu.edu> > From owner-chemistry@ccl.net Wed Sep 14 16:30:41 2005 From: "CCL" To: CCL Subject: CCL: W:Y zeolite coordinates needed Message-Id: <-29159-050914153232-6154-2NbaQmdzjXHCm+8GjNpz2w##server.ccl.net> X-Original-From: "James J. P. Stewart" Content-Type: multipart/alternative; boundary="=====================_24196823==.ALT" Date: Wed, 14 Sep 2005 12:56:29 -0600 Mime-Version: 1.0 Sent to CCL by: "James J. P. Stewart" [jstewart##us.fujitsu.com] --=====================_24196823==.ALT Content-Type: text/plain; charset="us-ascii"; format=flowed I have coordinates for Faujasite, in CIF, ENT and MOPAC data set forms. But what address do you want them sent to? The address "walk!A!vm.uff.br" is not recognized by my E-mail. Best wishes, Jimmy At 11:52 AM 9/14/2005, you wrote: >Sent to CCL by: "Jos Walkimar Carneiro" [walk!A!vm.uff.br] >Does anybody has the cartesian coordinates of the T20 model of >faujasite (Y) zeolite? >Thank you >Walkimar Carneiro( ## ## ) .-----------------oOOo----(_)----oOOo-------------------------------------. | James J. P. Stewart | | | Stewart Computational Chemistry LLC | E-mail: jstewart##us.fujitsu.com | | 15210 Paddington Circle | 39/03/15 N, 104/49/29 W | | Colorado Springs CO 80921-2512 | | | USA .ooo0 | Phone: USA +(719) 488-9416 | | ( ) Oooo. | | .------------------------\ (----( )-------------------------------------. \_) ) / (_/ --=====================_24196823==.ALT Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable I have coordinates for Faujasite, in CIF, ENT and MOPAC data set forms.

But what address do you want them sent to? The address "walk!A!vm.uff.br" is not recognized by my E-mail.

Best wishes,

Jimmy

At 11:52 AM 9/14/2005, you wrote:

Sent to CCL by: "Jos Walkimar Carneiro" [walk!A!vm.uff.br]
Does anybody has the cartesian coordinates of the T20 model of faujasite (Y) zeolite?
Thank you
Walkimar Carneiro

-=3D This is automatically added to each message by the mailing script =3D- and send your message to: CHEMISTRY##ccl.net
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.-----------------oOOo----(_)----oOOo---------------------------------= ----.
| James J. P. Stewart           &nb= sp;     |            &nb= sp;            &= nbsp;         |
| Stewart Computational Chemistry LLC | E-mail: jstewart##us.fujitsu.com |
| 15210 Paddington Circle           &nbs= p; | 39/03/15 N, 104/49/29 W          |
| Colorado Springs CO 80921-2512      |            &nb= sp;            &= nbsp;         |
| USA            &= nbsp;      .ooo0         | Phone: USA +(719) 488-9416        |
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            &nbs= p;            &n= bsp;       (_/ --=====================_24196823==.ALT-- From owner-chemistry@ccl.net Wed Sep 14 18:18:54 2005 From: "CCL" To: CCL Subject: CCL: Basis set for B3LYP Message-Id: <-29160-050914174400-13373-2NbaQmdzjXHCm+8GjNpz2w{:}server.ccl.net> X-Original-From: Antonio Hernandez Content-Type: multipart/alternative; boundary="----=_Part_2408_33047775.1126730338989" Date: Wed, 14 Sep 2005 13:38:58 -0700 Mime-Version: 1.0 Sent to CCL by: Antonio Hernandez [pescaomayor{:}gmail.com] ------=_Part_2408_33047775.1126730338989 Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Content-Disposition: inline Dear Tsuru: In theory, you can use any contracted or uncontracted Gaussian basis set= =20 with B3LYP functional calculations. Nevertheless, mostly all these basis=20 sets were optimized at the HF level of theory (or HF+correlation level).=20 For consistency, I would prefer to use basis sets optimized at the Density= =20 Functional Theory level of theory, as those described by Salahub in: N. Godbout, D. R. Salahub, J. Andzelm and E. Wimmer, Can. J. Chem. 70=20 (1992) 560.=20 You can get these at the website=20 http://www.emsl.pnl.gov/forms/basisform.html under DZVP(DFT Orbital) , DZVP2(DFT orbital) and TZVP(DFT Orbital) or=20 DGauss Polarized DFT Orbitals Basis Sets. I have personally obtained excellent results with this DFT + Salahub basis= =20 sets combination=20 (see for instance: Theor. Chem. Acc. 106 (2001) 218).=20 Best Whishes: Antonio Hernandez. =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D On 9/13/05, CCL wrote:=20 >=20 >=20 > Sent to CCL by: errol lewars [elewars-$-trentu.ca ] > 2005 Sept 14 >=20 > Hello, >=20 > The B3LYP functional is normally used with the 6-31G* basis set or > higher (e.g. 6-31G**, 6-311G*--of course there are other basis sets > besides these Pople sets; the Dunning correlation-consistent sets are > also popular). It is generally thought that the use of a smaller basis > with a correlated method (DFT or correlated ab initio) is pointless, but > I know of no definitive study of this. >=20 > A rare case of B3LYP/3-21G is the calc. of IEs of carbenes by > optimization at this level followed by B3LYP/6-31+G* single point > energies: H M Muchall et al., Can J Chem, 1998, 76, 221. The 3-21G basis > was better than the 6-31G* with CASSCF (not a DFT method) in a study of > the Cope rearrangement: D A Hrovat et al., J Am Chem Soc, 1999, 121, 169. >=20 > E. Lewars > =3D=3D=3D >=20 >=20 >=20 > CCL wrote: >=20 > >Sent to CCL by: "Telkuni Tsuru" [telkuni : venus.dti.ne.jp > ] > >Hello, CCLers. > > > >I like to know suitable basis set level for B3LYP on G98W. > > > >For example, MP2 calculation should not be carried out with > >low level basis set(e.g. STO-3G). So I like to know lowest basis > >set for B3LYP. Is "B3LYP/STO-3G" possible ? > > > > All responses, I will appreciate. > > I will summarize them and send to CCL. > > > > > > Thanks in advance > >--------------------------------------------------- > > Telkuni Tsuru telkuni{:}venus.dti.ne.jp> > > > > > > > > >=20 >=20 >=20 > -=3D This is automatically added to each message by the mailing script = =3D- > To send e-mail to subscribers of CCL put the string CCL: on your Subject:= =20 > line>=20 > Send your subscription/unsubscription requests to:=20 > CHEMISTRY-REQUEST{:}ccl.net>=20 > If your is mail bouncing from ccl.net domain due to spam= =20 > filters, please>=20 >=20 >=20 > ------=_Part_2408_33047775.1126730338989 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: quoted-printable Content-Disposition: inline
Dear Tsuru:

In theory, you can use any contracted or uncontracted Gaussian basis s= et with B3LYP functional calculations. Nevertheless, mostly all = these basis sets were optimized at the HF level of theory (or HF+correlatio= n level).=20

For consistency, I would prefer to use basis sets optimized at the Den= sity Functional Theory level of theory, as those described by Salahub in:

N. Godbout, D. R. Salahub, J. Andzelm and E. Wimmer, Can. J. Chem. 70 = (1992)  560.



   You can get these at the website

    http://www.emsl.pnl.gov/forms/basisfor= m.html

    under DZVP(DFT Orbital) , DZVP2(DFT orbital) and TZ= VP(DFT Orbital) or DGauss Polarized     DFT Orbitals Ba= sis Sets.

I have personally obtained excellent results with this DFT + Sal= ahub basis sets combination

(see for instance: Theor. Chem. Acc. 106 (2001) 218).  = ;            &n= bsp;            = ;

Best Whishes: Antonio Hernandez.

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D= =3D=3D=3D=3D=3D

On 9/13/05, = CCL <owner-chemistry{:}ccl.= net> wrote:

Sent to CCL by: errol lewars= [elewars-$-trentu.ca]
2005 Sept 14
=
Hello,

The B3LYP functional is normally used with the 6-31G* basis s= et or
higher (e.g. 6-31G**, 6-311G*--of course there are other basis set= s
besides these Pople sets; the Dunning correlation-consistent sets are
also popular). It is generally thought that the use of a smaller basis<= br>with a correlated method (DFT or correlated ab initio) is pointless, but=
I know of no definitive study of this.

A rare case of B3LYP/3-21= G is the calc. of IEs of carbenes by
optimization at this level followed by B3LYP/6-31+G* single point
en= ergies: H M Muchall et al., Can J Chem, 1998, 76, 221. The 3-21G basis
w= as better than the 6-31G* with CASSCF (not a DFT method) in a study of
the Cope rearrangement: D A Hrovat et al., J Am Chem Soc, 1999, 121, 169.
E. Lewars
=3D=3D=3D

CCL wrote:

>Sent to C= CL by: "Telkuni Tsuru" [telkuni : venus.dti.ne.jp]
>Hello, CCLers.
>
>I like to know su= itable basis set level for B3LYP on G98W.
>
>For example, MP2 c= alculation should not be carried out with
>low level basis set(e.g . STO-3G). So I like to know lowest basis
>set for B3LYP. Is "B3= LYP/STO-3G" possible ?
>
>  All responses, I wil= l appreciate.
>  I will summarize them and send to CCL.
= >
>
>  Thanks in advance
>----------------------------------= -----------------
>       Telkuni Tsuru=      telkuni= {:}venus.dti.ne.jp>
>
>
>
>

-=3D This is automatically added to each message by the mailing= script =3D-
To send e-mail to subscribers of CCL put the string CCL: on= your Subject: line
and send your message to:   CHEMISTRY{:}ccl.net

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------=_Part_2408_33047775.1126730338989-- From owner-chemistry@ccl.net Wed Sep 14 18:18:54 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29161-050914181652-22972-2NbaQmdzjXHCm+8GjNpz2w^^server.ccl.net> X-Original-From: "Cristian Bologa" Content-Disposition: inline Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=US-ASCII Date: Wed, 14 Sep 2005 15:35:40 -0600 Mime-Version: 1.0 Sent to CCL by: "Cristian Bologa" [cbologa^^salud.unm.edu] Dear Sandeep, Please take a look at this review published last year: Baber, J. C.; Feher, M. Predicting synthetic accessibility: application in drug discovery and development. Mini-Reviews in Medicinal Chemistry (2004), 4(6), 681-692. Regards, Cristian Bologa, Ph.D. Research Scientist Division of Biocomputing, Univ. of New Mexico, School of Medicine, MSC11 6145, Research Incubator Building, 2703 Frontier NE, Albuquerque, NM, 87131 tel: +1-505-272-6509 fax:+1-505-272-0238 >>> owner-chemistry^^ccl.net 09/14/05 8:19 AM >>> Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] Dear CCLers: I need some advice about the drug discovery/design. Using structure based design, one could develope several potential small molecular inhibitors/drugs for a given protein target. Many of these compounds may appear very attractive as they satisfy all lipinski's rules and your requirements for selectivity/specificity and may even have desirable solubility/ADME profiles. These days its possible to incorporate all these features right at the computational design stage. However, the organic synthesis of the compound still remains a bottleneck as it turns out that many of the designed compounds are 'hard' to synthesize or may require many steps of synthesis. I was wondering if there are some simple guidelines in the form of literature or 'hands on' experience available which could tell the computational/medicinal chemist whether a designed compound would be easy or hard to synthesize before he/she talks to the organic chemist. All your responses are greatly appreciated. Yours sincerely Sandeep Kumar, Ph.D. Johns Hopkins University, Dept. of Biology, 106 Mudd Hall, 3400 N. Charles St. Baltimore, MD 21218. Phone: 410-516-8433 Email: kumarsan^^jhu.edu From owner-chemistry@ccl.net Wed Sep 14 18:28:49 2005 From: "CCL" To: CCL Subject: CCL: Computational drug design blues Message-Id: <-29162-050914182335-30953-2NbaQmdzjXHCm+8GjNpz2w]-[server.ccl.net> X-Original-From: "Phil Hultin" Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset="us-ascii" Date: Wed, 14 Sep 2005 17:23:25 -0500 MIME-Version: 1.0 Sent to CCL by: "Phil Hultin" [hultin]-[cc.umanitoba.ca] I note that the question of assessing the "ease of synthesis" has excited a fair bit of comment. As I already pointed out, and as also stated by Gary Breton, the organic chemistry community does not think it is actually possible to meaningfully assess "ease of synthesis" by an algorithmic approach. To those who have mentioned various computer-aided synthesis planning software, let me simply ask: once you have a proposed synthetic route, how do you determine whether it is "easy" to put into practice or not? There have been many programs developed to seek synthetic pathways, but none has actually been able to differentiate unambiguously or consistently between "good" options and "bad" options. The number of steps or the average yield per step are not meaningful criteria in and of themselves, although they do enter into the assessment. Other issues that bear on the practicality question are (not a comprehensive list): > cost of raw materials > cost of solvents > cost of reagents, catalysts etc. > cost of disposal of waste materials > health and lab safety hazards associated with reagents, solvents and intermediate compounds > level of selectivity actually attainable (stereoselectivity, regioselectivity, chemoselectivity) > need for purification, particularly chromatography > solubilities, boiling points and other physical parameters > expected thermodynamic and kinetic stability of intermediates > scalability - can the proposed route be used only for milligram amounts or can it be implemented on gram or kilo scales as needed? The list could go on. The bottom line is that in order to determine whether a proposed drug candidate is actually practical, you need to consider numerous variables that cannot be reduced to a simple numerical scale. This is where the experience and expertise of the bench chemist is essential. Dr. Philip G. Hultin Associate Professor of Chemistry, University of Manitoba Winnipeg, MB R3T 2N2 hultin]-[cc.umanitoba.ca http://umanitoba.ca/chemistry/people/hultin -----Original Message----- > From: owner-chemistry]-[ccl.net [mailto:owner-chemistry]-[ccl.net] Sent: September 14, 2005 1:44 PM To: Hultin, Philip G. Subject: CCL: W:Computational drug design blues Sent to CCL by: Gary Breton [gbreton]"[berry.edu] Speaking as an organic chemist I can tell you that the answer to your question is probably no. There is no easy way to tell whether a given compound is easy or difficult to synthesize other than to give it to a medicinal or organic chemist that has experience in and knows synthesis. For example, a compound with a nitro group at one position may be very easy to synthesize, but move it over one carbon and suddenly you have a very difficult system to synthesize. Any "simple" guidelines would probably not differentiate between the difficulty in synthesis of these types of isomers. While there have been attempts at generating software to aid in "deconstructing" molecules towards the goal of making planned syntheses easier, none of these (at least to my knowledge) is particular robust. I have never heard of an organic chemist...or seen cited in a paper...the use of such software to aid in a synthetic route. While there may be exceptions, it certainly isn't the norm. ..and I don't say all this just for the sake of job security ;) Gary W. Breton Associate Professor Hard-Working Organic Chemist Department of Chemistry Berry College PO Box 495016 Mount Berry, GA 30149 > Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] > Dear CCLers: > > I need some advice about the drug discovery/design. Using structure based > design, one could develope several potential small molecular inhibitors/drugs > for a given protein target. Many of these compounds may appear very attractive > as they satisfy all lipinski's rules and your requirements for > selectivity/specificity and may even have desirable solubility/ADME profiles. > These days its possible to incorporate all these features right at the > computational design stage. However, the organic synthesis of the compound > still remains a bottleneck as it turns out that many of the designed compounds > are 'hard' to synthesize or may require many steps of synthesis. I was > wondering if there are some simple guidelines in the form of literature or > 'hands on' experience available which could tell the computational/medicinal > chemist whether a designed compound would be easy or hard to synthesize before > he/she talks to the organic chemist. > > All your responses are greatly appreciated. > > Yours sincerely > Sandeep Kumar, Ph.D. > Johns Hopkins University, > Dept. of Biology, > 106 Mudd Hall, > 3400 N. Charles St. > Baltimore, MD 21218. > Phone: 410-516-8433 > Email: kumarsan]-[jhu.edu From owner-chemistry@ccl.net Wed Sep 14 20:36:10 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29164-050914201446-8164-ETc9kVj+VqHwexQEb/3djg{:}server.ccl.net> X-Original-From: Andrew Fant Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=ISO-8859-1 Date: Wed, 14 Sep 2005 18:15:50 -0400 MIME-Version: 1.0 Sent to CCL by: Andrew Fant [fant{:}pobox.com] By any chance, can you give a pointer into the literature on that index? I'm not able to get into chemical abstracts at the moment, but both google and google scholar had no hits at all on "synthetic feasibility index" Thanks, Andy CCL wrote: > Sent to CCL by: "Srinivasan Parthiban" [parthiban-#-gvkbio.com] > There must be few programs available on estimating the Synthetic > feasibility Index. I have used it few years back using Tripos software. It > is purely an empirical method where the calculation is based on the number > of rings and the functional groups present in the molecule and so on. > - Parthi > ----------------------------------- > Srinivasan Parthiban > Director-Informatics > GVKBIO > Vukan Towers > #81 Tirumalai Pillai Road > T. Nagar, Chennai 600 017 INDIA > Ph: +91-44-5212 5522/3399 > www.gvkbio.com From owner-chemistry@ccl.net Wed Sep 14 20:36:10 2005 From: "CCL" To: CCL Subject: CCL: W:Computational drug design blues Message-Id: <-29163-050914185629-18100-ETc9kVj+VqHwexQEb/3djg/a\server.ccl.net> X-Original-From: "Baber, Christian" Content-Class: urn:content-classes:message Content-Type: multipart/mixed; boundary="_-==6F36405529436605==-_" Date: Wed, 14 Sep 2005 15:10:36 -0700 MIME-Version: 1.0 Sent to CCL by: "Baber, Christian" [cbaber/a\neurocrine.com] --_-==6F36405529436605==-_ Content-Type: text/plain; charset=iso-8859-1 Content-Transfer-Encoding: quoted-printable As other people have mentioned estimating synthetic accessibility is a = difficult problem particularly when considering compounds designed by = people or computers with little knowledge of synthetic chemistry.=20 A number of groups working on de novo design programs have attempted to = include synthetic accessibility in their systems to various levels. = These include SPROUT (from Peter Johnson's group in Leeds) and SkelGen = (from Denovo Pharmaceuticals). There have also been a number of methods = applied to estimating synthetic accessibility including expert systems = (CAESA, again from Leeds) and neural networks (Takaoka et al, JCICS, = 2003, 42, 1269-1275). We recently wrote a review paper on the subject = (Mini-Reviews in Medicinal Chemistry, Volume 4, No. 6, 2004, 681-692) = which covers a wide range of techniques and uses. This is certainly an important area and anything that that could = reliably stop us suggesting synthetically infeasible compounds to = medicinal chemists would be very welcome. Best of luck, Christian > -----Original Message----- > From: CCL [mailto:owner-chemistry/a\ccl.net] > Sent: Wednesday, 14 September, 2005 7:10 AM > To: Baber, Christian > Subject: CCL: W:Computational drug design blues >=20 >=20 >=20 > Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] > Dear CCLers:=20 >=20 > I need some advice about the drug discovery/design. Using=20 > structure based design, one could develope several potential=20 > small molecular inhibitors/drugs for a given protein target.=20 > Many of these compounds may appear very attractive as they=20 > satisfy all lipinski's rules and your requirements for=20 > selectivity/specificity and may even have desirable=20 > solubility/ADME profiles. These days its possible to=20 > incorporate all these features right at the computational=20 > design stage. However, the organic synthesis of the compound=20 > still remains a bottleneck as it turns out that many of the=20 > designed compounds are 'hard' to synthesize or may require=20 > many steps of synthesis. I was wondering if there are some=20 > simple guidelines in the form of literature or 'hands on'=20 > experience available which could tell the=20 > computational/medicinal chemist whether a designed compound=20 > would be easy or hard to synthesize before he/she talks to=20 > the organic chemist. >=20 > All your responses are greatly appreciated. >=20 > Yours sincerely > Sandeep Kumar, Ph.D.=20 > Johns Hopkins University, > Dept. of Biology,=20 > 106 Mudd Hall,=20 > 3400 N. Charles St.=20 > Baltimore, MD 21218.=20 > Phone: 410-516-8433 > Email: kumarsan/a\jhu.edu >=20 >=20 >=20 > -=3D This is automatically added to each message by the mailing=20 > script =3D- > To send e-mail to subscribers of CCL put the string CCL: on=20 > your Subject: line>=20 > Send your subscription/unsubscription requests to:=20 > CHEMISTRY-REQUEST/a\ccl.net=20 > HOME Page: http://www.ccl.net | Jobs Page: http://www.ccl.net/jobs=20 >=20 > If your is mail bouncing from ccl.net domain due to spam=20 > filters, please > use the Web based form from CCL Home Page=20 > -+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ > -+-+-+-+-+ >=20 >=20 >=20 >=20 --_-==6F36405529436605==-_ Content-Type: text/plain; charset=iso-8859-1; name=mmsinfo.txt Content-Transfer-Encoding: 7bit Content-Disposition: attachment; filename=mmsinfo.txt "MMS " made the following annotations on 09/14/2005 03:10:39 PM ------------------------------------------------------------------------------ This email may contain confidential and privileged material for the sole use of the intended recipient. Any review or distribution by others is strictly prohibited. If you are not the intended recipient, please contact the sender and delete all copies. ============================================================================== --_-==6F36405529436605==-_-- From owner-chemistry@ccl.net Wed Sep 14 22:57:52 2005 From: "CCL" To: CCL Subject: CCL: W:single crystal X-ray diffraction simulator Message-Id: <-29166-050914210223-27473-ETc9kVj+VqHwexQEb/3djg{}server.ccl.net> X-Original-From: "Constantinos Zeinalipour-Yazdi" Sent to CCL by: "Constantinos Zeinalipour-Yazdi" [czeinali{}chem.ucsd.edu] Greetings, everyone, I am looking for a free software that can simulate single crystal X-ray diffraction patterns given the unit cell parameters and the cartesian or fractional coordinates of the symmetry unique atoms in the unit cell. Preferable in .CIF format but other formats are also welcome. The program should be windows or linux compatible. Any suggestions are welcome. best wishes, Constantinos From owner-chemistry@ccl.net Wed Sep 14 22:57:52 2005 From: "CCL" To: CCL Subject: CCL: Computational drug design blues Message-Id: <-29165-050914215937-10257-ETc9kVj+VqHwexQEb/3djg]^[server.ccl.net> X-Original-From: Steve Bowlus Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=ISO-8859-1; format=flowed Date: Wed, 14 Sep 2005 18:59:17 -0700 MIME-Version: 1.0 Sent to CCL by: Steve Bowlus [chezbowlus]^[goldrush.com] I will add to Prof. Hultin's list. One is generally not in the position of doing a one-off synthesis of a silver bullet (our prowess at designing same notwithstanding ;-). As a practical matter in medicinal chemistry, additional consideration must be given to - whether a synthetic route will allow reasonable variations to be prepared; - whether a route is amenable to parallel synthetic strategies. Generally the synthesis/medicinal chemist must be concerned with preparation of sets of congeners in order to determine structure-activity relationships (or more generally property-performance relationships). It is one thing to do a total synthesis of vitamin B-12 (as did R.B. Woodward). It is something else again to have a route that allows synthesis of B-12, heme, and chlorophyll by substantially the same method. Cheers, Steve CCL wrote: > Sent to CCL by: "Phil Hultin" [hultin]-[cc.umanitoba.ca] > I note that the question of assessing the "ease of synthesis" has excited a > fair bit of comment. As I already pointed out, and as also stated by Gary > Breton, the organic chemistry community does not think it is actually > possible to meaningfully assess "ease of synthesis" by an algorithmic > approach. > > To those who have mentioned various computer-aided synthesis planning > software, let me simply ask: once you have a proposed synthetic route, how > do you determine whether it is "easy" to put into practice or not? > > There have been many programs developed to seek synthetic pathways, but none > has actually been able to differentiate unambiguously or consistently > between "good" options and "bad" options. The number of steps or the > average yield per step are not meaningful criteria in and of themselves, > although they do enter into the assessment. Other issues that bear on the > practicality question are (not a comprehensive list): > >>cost of raw materials >>cost of solvents >>cost of reagents, catalysts etc. >>cost of disposal of waste materials >>health and lab safety hazards associated with reagents, solvents and > > intermediate compounds > >>level of selectivity actually attainable (stereoselectivity, > > regioselectivity, chemoselectivity) > >>need for purification, particularly chromatography >>solubilities, boiling points and other physical parameters >>expected thermodynamic and kinetic stability of intermediates >>scalability - can the proposed route be used only for milligram amounts or > > can it be implemented on gram or kilo scales as needed? > > The list could go on. The bottom line is that in order to determine whether > a proposed drug candidate is actually practical, you need to consider > numerous variables that cannot be reduced to a simple numerical scale. This > is where the experience and expertise of the bench chemist is essential. > > Dr. Philip G. Hultin > > Associate Professor of Chemistry, > > University of Manitoba > > Winnipeg, MB > > R3T 2N2 > > hultin]^[cc.umanitoba.ca > > http://umanitoba.ca/chemistry/people/hultin > > > -----Original Message----- > >>From: owner-chemistry]^[ccl.net [mailto:owner-chemistry]^[ccl.net] > > Sent: September 14, 2005 1:44 PM > To: Hultin, Philip G. > Subject: CCL: W:Computational drug design blues > > > Sent to CCL by: Gary Breton [gbreton]"[berry.edu] > Speaking as an organic chemist I can tell you that the answer to your > question is probably no. There is no easy way to tell whether a given > compound is easy or difficult to synthesize other than to give it to a > medicinal or organic chemist that has experience in and knows synthesis. > For example, a compound with a nitro group at one position may be very easy > to synthesize, but move it over one carbon and suddenly you have a very > difficult system to synthesize. Any "simple" guidelines would probably not > differentiate between the difficulty in synthesis of these types of isomers. > While there have been attempts at generating software to aid in > "deconstructing" molecules towards the goal of making planned syntheses > easier, none of these (at least to my knowledge) is particular robust. I > have never heard of an organic chemist...or seen cited in a paper...the use > of such software to aid in a synthetic route. While there may be > exceptions, it certainly isn't the norm. > > .and I don't say all this just for the sake of job security ;) > > > Gary W. Breton > Associate Professor > Hard-Working Organic Chemist > Department of Chemistry > Berry College > PO Box 495016 > Mount Berry, GA 30149 > > > > > > >>Sent to CCL by: "Sandeep Kumar" [kumarsan\a/jhu.edu] >>Dear CCLers: >> >>I need some advice about the drug discovery/design. Using structure based >>design, one could develope several potential small molecular > > inhibitors/drugs > >>for a given protein target. Many of these compounds may appear very > > attractive > >>as they satisfy all lipinski's rules and your requirements for >>selectivity/specificity and may even have desirable solubility/ADME > > profiles. > >>These days its possible to incorporate all these features right at the >>computational design stage. However, the organic synthesis of the compound >>still remains a bottleneck as it turns out that many of the designed > > compounds > >>are 'hard' to synthesize or may require many steps of synthesis. I was >>wondering if there are some simple guidelines in the form of literature or >>'hands on' experience available which could tell the > > computational/medicinal > >>chemist whether a designed compound would be easy or hard to synthesize > > before > >>he/she talks to the organic chemist. >> >>All your responses are greatly appreciated. >> >>Yours sincerely >>Sandeep Kumar, Ph.D. >>Johns Hopkins University, >>Dept. of Biology, >>106 Mudd Hall, >>3400 N. Charles St. >>Baltimore, MD 21218. >>Phone: 410-516-8433 >>Email: kumarsan]^[jhu.edu> > > > > > From owner-chemistry@ccl.net Wed Sep 14 23:14:26 2005 From: "CCL" To: CCL Subject: CCL: W:Disclose your data, or not publish ! Message-Id: <-29167-050914231333-32392-ETc9kVj+VqHwexQEb/3djg|"|server.ccl.net> X-Original-From: "Chemical Bond" Sent to CCL by: "Chemical Bond" [chemicalbond001|"|yahoo.com] Everyday, tons of new publications come out. Although there are some nice papers with novel ideas or new results, many times we see people are almost trying to repeat others' work, pouring the same water into the old bottle. The only goal for that seems to be just publishing, for tenure in academia or for promotion in industry, or for boasting some software! One obvious case is in the community of protein-ligand docking & scoring. Are not we tired of those studies? Yes, we are! We always see extremely excellent results published in papers or ACS talks by different kinds of people, especially those who made software and make money! The reality is that none of them really works! Not at all! Ask anyone in a big pharma doing docking & scoring business, see what you would get the performance for a scoring function applied in a real drug design case? That's all about business, to keep software company making money and keep computational chemists' in jobs. Fine, but in order to promote the advancement of science, we had better do something novel than that. I hope people in this list could make more suggestions, and here I like to propose a little to the community: To disclose your data, or not publish. (1)Disclose all numerical data files, input, output files & parameters in the publication (paper or talk), in the sense that at least it could be reproduced (statistically meaningful) if anyone else is trying to do it using the same software or method. So no one can be lying any more. (2)This could save much time for many other researchers on preparing testing data, so that new ideas could get tested & improved very quickly; (3)This could help build a very rich resource for research, things like docking decoys for many many protein targets and ligands; the data itself would be worth a million dollars ?! ... ... All in all, theose really good methods or software will survive without questions, and new technologies would evolve in the speed-of-light, we would see fewer but more meaningful new papers every day, what a relif from tons of new electronic papers... ... so that in the end science would get advanced by taking advantage of everyone's strength, and life could be improved in a different way...... Thanks for your attention! -Bond