From mmconn@esau.mit.edu Wed Sep 8 04:12:09 1993 Date: Wed, 8 Sep 93 08:12:09 -0400 From: mmconn@esau.mit.edu (morgan conn) Message-Id: <9309081212.AA21168@esau.mit.edu> To: chemistry@ccl.net Subject: Re: drug modeling Hi everyone, It seems my message of yesterday is stuttering a bit. Sorry about that - I didn't do anything! Honest! -mmc ********************************************************* Morgan Conn MIT Chemistry, 18-148, Cambridge, MA 02139; mmconn@esau.mit.edu, 617.253.6438, 617.253.7929 (fax) ********************************************************* From avkampen@sci.kun.nl Wed Sep 8 16:38:02 1993 Date: Wed, 8 Sep 1993 14:38:02 +0200 From: "A. van Kampen" Message-Id: <199309081238.AA21608@wn1.sci.kun.nl> To: CHEMISTRY@ccl.net Subject: Wanted: local optimization algorithms in C Hello, I'm looking for local optimization methods (Newton methods, Gradient methods, conjugated gradient methods etc) written in C. Does any one know if any source code (and documentation) is available? Thanks, -------------------------------------------------------- | Antoine van Kampen | | University of Nijmegen | | Laboratory for Analytical Chemistry | | Faculty of science | | Toernooiveld 1 | | 6525 ED Nijmegen | | the Netherlands | | | | Email: avkampen@sci.kun.nl | -------------------------------------------------------- From ruusvuor@csc.fi Wed Sep 8 17:53:57 1993 Date: Wed, 8 Sep 1993 14:53:57 +0300 (EET) From: Raimo Uusvuori Subject: Re: drug modeling To: morgan conn Message-Id: On Tue, 7 Sep 1993, morgan conn wrote: > > A couple of weeks ago I posted a request for information on the modeling/ > handling/design of drugs. Here are the results: > At least one commercial molecular modelling package was missing, namely Chem-X: Europe: Chemical Design Ltd, Roundway House, Cromwell Park, Chipping Norton, Oxon OX7 5SR, UK, Tel: (0608) 644 000, Fax: (0608)642 244 North America: Chemical Design Inc., Suite 120, 200 Route 17 South, Mahwah, New Jersey 07430, USA, Tel: (201) 529 3323, Fax: (201) 529 2443 In addition to normal molecular modelling modules for display, motion, reading and writing, energy and geometry calculations, quantum mechanics, (there are interfaces to third party programs), molecular fitting, maps, surfaces, and conformational analysis Chem-X contains modules for databases, QSAR, proteins and peptides, polymers, and crystals. Raimo Uusvuori ------------------------------------------------------------------------ Raimo Uusvuori | Phone: +358-0-457 3210 Scientific Software Specialist | FAX: +358-0-457 2302 Chemistry | | Center for Scientific Computing | Street address: P.O. Box 405 | Tietotie 6, FIN-02150 ESPOO FIN-02101 ESPOO | E-mail: ruusvuor@csc.fi FINLAND | Raimo.Uusvuori@csc.fi ------------------------------------------------------------------------ From scsupham@reading.ac.uk Wed Sep 8 09:41:02 1993 From: scsupham@reading.ac.uk Date: Wed, 8 Sep 93 10:29:49 BST Message-Id: <2482.9309080929@scsscsc3> To: chemistry@ccl.net Subject: SUMMARY of MP2 opt problem ---------- X-Sun-Data-Type: text X-Sun-Data-Description: text X-Sun-Data-Name: text X-Sun-Content-Lines: 402 Hi G92 users, Many people made helpful suggestions about my problem optimising the geometry of thiophne at the MP2 level. Ive collated the replies below. Ive givven Doug Fox's reply first since, I guess, this is the `official' response. Thanks for all your help. john upham cut here--- >From fox@edu.cmu.chem.cmchem Thu Sep 2 20:27:35 1993 John, the problem is with your route. You have specified MP2 twice and it is giving you an MP4 optimization not MP2. As a result you are using the FP optimizer which only uses energies not gradients. Each cycle is on one coordinate only and needs 3 points ... I think you get the point. What you want is #P MP2=Stingy/3-21G** SCF=Direct FOpt to do an MP2 geometry opt with all the options you requested. Let me comment further, MP2=Stingy only affect MP2 frequency calculations so you can leave that off. FOPT is a good idea, it does not change the optimization algorithm but adds a check to see that your coordinates are really independent and span the space you are optimizing in. The only thing I would add would be to run the HF frequencies first and read in that force constant matrix, FOPT=RCFC, from the checkpoint file. The force constants are quite transferable between bases and methods. As to cartesians vs. internals, this is currently a debate best left to angels. If you have a good Z-matrix, and yours looks fine, it will be at least as fast as a cartesian optimizer. There was a fine exposition of this on the net yesterday, diagonal Hessians etc. If you have cartesians and don't have the expertise to make a good Z-matrix then it is probably better to try and use cartesians. In your case it is quite easy to set up a cartesian description, all atoms in the XY plane, S on the X axix and the two carbons bonded to S on the Y axis. Then you can have symmetric variables for the cartesians and force Z=0.0. this freezes out the rotation and gives you a minimum number of variables with a nearly diagonal Hessian. Thus stiff, flat rings are a good case for cartesians. With G92 you can even define the ring in cartesians and add substituents with internals to get the best of both worlds. The cases which remain hard are floppy rings where internals help to make the Hessian diagonal but cartesians are far easier to define the system. My closing comment is why did you choose 3-21G** as the basis? You should consider moving to MP2/6-31G* or 6-31G** to really get the correlation as opposed to basis set incompleteness. Doug >From klemm@edu.msc Thu Sep 2 17:20:39 1993 Chances are really good that you would be better off with cartesians for the ring atoms of this system. If you look at the geometry optimization steps as an animation, you'll probably see the ring sort of jerking around, especially the bond that isn't explicitly defined in the Z-matrix. --Stefan >From milan@gov.nih.helix Thu Sep 2 17:55:59 1993 Hi John, Try the Z-matrix below. It should be done in just a few steps. I fixed the symmetry to C2v, but if for any reason you want to relaxe this you may do so within the same Z-matrix definition! Good luck! -- Milan Hodoscek $ RunGauss #p rMP2/3-21G** SCF=DIRECT fopt MP2=stingy thiophene geometry opt using the MP2 level of theory C2v symm. fixed (may be also relaxed) [starting from AM1 geom.] 0 1 x s 1 r2 c 1 r3 2 a3 c 1 r3 2 a3 3 d3 x 1 r5 3 a5 2 d5 c 5 r6 1 a6 3 d6 c 5 r6 1 a6 4 d6 h 3 r8 2 a8 1 d8 h 4 r8 2 a8 1 d8 h 6 r10 3 a10 1 d10 h 7 r10 4 a10 1 d10 r2 1.1410 r3 1.2284 r5 1.2701 r6 0.7219 r8 1.0864 r10 1.0917 a8 120.3421 a10 125.6796 a3 90.0000 a5 90.0000 a6 90.0000 d3 180.0000 d5 180.0000 d6 0.0000 d8 180.0000 d10 180.0000 >From fagerbur@com.kodak Thu Sep 2 18:19:24 1993 John, It would appear that your problem is likely that your choice of Z-matrix causes the C4-C5 bond length to vary wildly with small changes in the r's or a's for the other heavy atom parts of the molecule - i.e., there is a coupling of values in the Z-matrix. This is a classical problem with a ring system such as benzene. The solution the Gaussian people give in their class is to define a dummy atom in the center of the ring and one perpendicular to it and the desired ring plane. This, according to them will remove the coupling and allow optimization of the structure. I have not tried it but supposedly it works. Incidently, asking for fopt does not really do anything differently except that it checks to see if you have enough degrees of freedom - sorry - enough variables for the degrees of freedom of the molecule. For your molecule you have of course imposed symmetry whereas there exists a possibility that the calculation could find a somewhat lower energy of a lower symmetry structure. (Yes, I know the actual molecule is the symmetry you have) So in that sense you may not have enough variables to ensure the fully optimized structure. Lots of luck. David Fagerburg fagerbur@kodak.com >From elewars@ca.utoronto.chem.alchemy Thu Sep 2 18:37:06 1993 Two points occur to me about your attempted MP2 opt: 1. Geometry optimizations of cyclic compounds using Z-matrices can fail if the ring atoms are defined sequentially, due to an error ratcheting effect; this does not seem to be a problem with your Z-mat, but you might still try using a dummy atom: S1 X2 S1 X2S1 C3 X2 C3X2 S1 a321 C4 C3 C4C3 X2 a432 S1 d4321 C5 X2 C3X2 S1 a321 C3 d5213 C6 C5 C4C3 etc This is only an idea; I understand that it can be difficuklt to find a good Z-mat for cyclic systems (one that starts off with an almost diagonal hessian). Cartesians, I've been told, are better than a poor Z-mat. 2. Optimizations, particularly if cart's are being used, go faster if a good initial hessian huess is available. It may be a good idea to do a HF level (not MP)/sto-3g opt starting from any reasonable geom, (or maybe because of the S, sto-3g* or 3-21g*), then use the hessian (& wavefunction) from that as a starting point for the MP2 job. I notice you specify the 3-21G** basis; this is unusual for MP2, which is usually done with 6-31G* (occasionally bigger). In any case, try a low-level calc for a start, and feed its output into your MP2 calc. Three papers of interest are: Geometry optimization in Cartesian coordinates: The end of the Z-matrix, J. Baker, W. J. Hehre, J Comp. Chem. (1991) 12:5, 606. Geometry optimization in Cartesian coordinates, J. Baker, J. Comp. Chem. (1992) 13:2, 240. Technique for geometry optimization: a comparison of Cartesian and natural internal coordinates, J. Baker, J. Comput. Chem. (1993) 14:9 1085. It might be helpful to contact the gaussian people: help@gaussian.com I noticed you expressed an interest in the replies to my Cart's vs. Z-mat query of a few days ago. When I've sorted things out I shall post a summary of the information I received, since this seems to be a matter of fairly general interest. Good luck. Errol ============================ elewars@trentu.ca E. Lewars, Chem Dept Trent University, Peterborough Ontario, Canada K9J 7B8 ====================================== >From tshehla@za.ac.und.che Thu Sep 2 20:30:36 1993 Dear John; Out of the 63 cycles take the one with the lowest E(UMP2) energy, use its Z-matrix and restart the optimisation. You may get to convergence. If not; just keep taking the lowest energy Z matrix. But remember some jobs do not converge. T M Tshehla. (University of Natal. South Africa). >From dudisds@mil.af.wpafb.ml.picard Thu Sep 2 22:26:46 1993 John - We just did thiophene (and bithiophene) at the MP2/6-31G* level. Maybe we can share data (I'd certainly at least be interested in learning of your interest - we have been doing extensive CI's to get good excitation levels. ). Doug Dudis Polymer Branch Wright Patterson AFB >From chemistry-request@edu.osc Fri Sep 3 03:13:47 1993 First, have you attempted optimizing the geometry with a lower basis set using perhaps just HF optimization? The best thing to do is run a preliminary rhf run, with perhaps rhf/sto-3g to optimize the given microwave geometry. Second, using the option opt=readfc run the basis set you are using for MP2's (i.e. run an rhf/6-31g* or whatever basis it is you're using). Then, finally, run the MP2, and be sure to use opt=readfc, and a chkpoint file to take these force constants >from (i.e. the chk file from the previous rhf run). I hope this works for you. Rob From frj@dk.dou Fri Sep 3 07:03:34 1993 Date: 3 Sep 93 8:03 +0200 From: Frank Jensen To: scsupham@uk.ac.reading Subject: g92 mp2 opt John, Take your microwave structure, do a RHF/3-21G freq=noraman sleazy to get a good set of force constants (use a chk-file).Then do the MP2 optimization with a opt=readfc. Your problemis the large coupling elements in the Hessian for cyclic systems, you need a better than the usual diagonal guess for the hessian. And BTW, don't do MP2 with a 3-21G** basis, the sp-basis is too small, use the 6-31G** (or maybe just 6-31G*) instead, it only cost you a little more and gives much more reliable results. Frank From gene@com.cray.calv2 Fri Sep 3 20:40:39 1993 Date: Fri, 3 Sep 93 15:40:25 EDT From: gene@com.cray.calv2 (Eugene Fleischmann) John, One approach to solving this problem, (63 steps at the MP2 level is considerably expensive!), is to bootstrap the calculation up level by level. Perform geom. opt. at semi-empirical level with MM-based diagonal guess for initial Hessian; save checkpoint file. Read in Hessian, geometry, and project AM1 wavefunction onto ab initio basis from semi-empirical calculation and perform geom. opt. at RHF level with appropriate basis set; save checkpoint file. Read in geometry and initial guess for wavefunction from RHF optimization and perform second derivative analysis at optimized geometry to get good starting Hessian; save checkpoint file. Copy rhf checkpoint file to mp2 checkpoint file (in case there are any difficulties in the mp2 run, you can always restart from this point), and THEN IN A SEPARATE JOB -> Read in geometry, initial guess, and Hessian from rhf run, and begin MP2 geom. opt. run on Cray Y-MP time for first procedure (6 Steps) in first job: Job cpu time: 0 days 0 hours 0 minutes 8.7 seconds. time for second procedure (5 Steps) in first job: Job cpu time: 0 days 0 hours 5 minutes 30.2 seconds. time for third procedure (FREQ) in first job: Job cpu time: 0 days 0 hours 6 minutes 9.2 seconds. second job not run, except to check input i.e.GUESS=(Read,Only) Alternatively, one could just start the MP2 optimization with a GOOD guess at the Hessian by calculating it analytically at the start, but this is probably much more expensive and the optimization still depends on how good of a geometry that you started from. Input files follow. Gene ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ Eugene D. Fleischmann, Ph.D. Computational Chemist Cray Research, Inc. (609) 252-1250 121 Commons Way gene@calv2.cray.com Princeton, NJ 08540 ++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ %CHK=thio_rhf #P AM1 FCHK=ALL FOPT OPTCYC=20 SCF=(DIRECT,TIGHT) SCFCYC=64 upham.2.08.02.14.07.01; thiophene geom opt, AM1 opt 0 1 S C 1 r2 C 1 r2 2 a3 C 2 r4 1 a4 3 d4 C 3 r4 1 a4 2 d4 H 2 r6 1 a6 3 d6 H 3 r6 1 a6 2 d6 H 4 r8 2 a8 1 d6 H 5 r8 3 a8 1 d6 Variables: r2= 1.7140 a3= 92.09 r4= 1.3690 a4= 111.50 r6= 1.0780 a6= 119.80 r8= 1.0800 a8= 124.25 Constants: d4= 0.00 d6= 180.00 --Link1-- %CHK=thio_rhf #P RHF/3-21G** FCHK=ALL FOPT(MNDOFC) OPTCYC=20 SCF=(Direct,Tight) SCFCyc=64 Geom=CheckPoint Guess=CheckPoint upham.2.08.02.14.07.01; thiophene geom opt, RHF opt w/AM1 FC at start 0 1 --Link1-- %CHK=thio_rhf #P RHF/3-21G** FCHK=ALL FREQ SCF=(Direct,Tight) SCFCyc=64 Geom=CheckPoint Guess=CheckPoint upham.2.08.02.14.07.01; thiophene geom opt, RHF freq 0 1 ------------------------------------------------------------ cp thio_rhf.chk thio_mp2.chk ------------------------------------------------------------ %CHK=thio_mp2 #P MP2/3-21G** FCHK=ALL FOPT=ReadFC OPTCYC=20 SCF=(Direct,Tight) SCFCyc=64 Geom=CheckPoint Guess=CheckPoint upham.2.08.02.14.07.01; thiophene geom opt, MP2 opt w/RHF FC at start 0 1 ------------------------------------------------------------ >From @net.eu.britain,@uucp.kddlab:inoue@jp.co.greencross Sun Sep 5 05:58:30 1993 Dear Dr.John Upham: I think your z-matrix is easy to be made, but for computer it will be hard to be optimized faster. Then I show you one of the Z-matrix example which might be converged faster. 0 1 X X 1 1.0 S 1 r1 2 90.0 C 1 r2 2 90.0 3 d1 C 1 r2 2 90.0 3 d2 C 1 r3 2 90.0 3 d3 C 1 r3 2 90.0 3 d4 X 4 1.0 1 90.0 2 0.0 X 5 1.0 1 90.0 2 0.0 X 6 1.0 1 90.0 2 0.0 X 7 1.0 1 90.0 2 0.0 H 4 r6 8 90.0 1 180.0 H 5 r6 9 90.0 1 180.0 H 6 r8 10 90.0 1 d5 H 7 r8 11 90.0 1 d6 Variables: r1= 1.550 r2= 1.285 r3= 1.151 r6= 1.0780 r8= 1.0800 d1= 73.7 d2= -73.7 d3= 141.8 d4=-141.8 d5=-175.1 d6= 175.1 Because it depends only on distance and torsion angle. This torsion angle is not depend on the coordinate of the other atom! So it converges faster maybe. Please try this. Hope this help. Yoshihisa INOUE the Green Cross Corp. Shodai-Ohtani 2-25-1 Hirakata, 573 JAPAN inoue@greencross.co.jp ---------- X-Sun-Data-Type: mail-file X-Sun-Data-Description: mail-file X-Sun-Data-Name: thio_opt.msgs X-Sun-Encoding-Info: uuencode X-Sun-Content-Lines: 309 begin 600 thio_opt.msgs M1G)O;2!F;WA 961U+F-M=2YC:&5M+F-M8VAE;2!4:'4@4V5P(" R(#(P.C(W M.C,U(#$Y.3,*"B @2F]H;BP*"B @('1H92!P6]U MF%T:6]N(&YO="!-4#(N("!! 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Does anybody know of a proram/subroutines that may compute the magnetic dipole moment for paramagnetic transition metal coordination complexes, preferably using DFT, MCSCF, or MP2 etc densities/wavefunctions? POLYATOM apparently has a very extensive property package, but is this feature included? thanks gus mercier mercie@cumc.cornell.edu From jpj@lotus.medicine.rochester.edu Wed Sep 8 13:12:56 1993 Date: Wed, 8 Sep 93 13:12:56 GMT From: jpj@lotus.medicine.rochester.edu (Jeffrey P. Jones) Message-Id: <9309081312.AA12518@lotus.medicine.rochester.edu> To: CHEMISTRY@ccl.net Subject: Global min. in protein folding >This is a very good and topical question. It was proposed by >several speakers at a recent conference (MacroMolecules, Genes, >and Computers, Waterville Valley, N.H., Aug 1993) that proteins are >in a global minimum (at least small, compact, re-foldable proteins). >A good discussion is the paper by Ruben A. Abagyan, "Towards protein >folding by global energy optimization", FEBS 325, 17-22 (1993). >The idea at the meeting seemed to be that the force fields were >incomplete for proteins, and if the proper functions were used >(electrostatics, hydrophobicity, contact surface, entropy, etc) the true >free energy of the protein structure would be the global minimum. >I must admit I was surprised by these ideas, and had assumed (like >most other people I know) that proteins were in a local (but not >necessarily global) minimum. While I am not a protein folding person I have conducted an informal poll of protein folding folks and found that the above generalization is true. They all site the small proteins that refold as an example. If the protein cannot be refolded it is an experimental problem since it doesn't agree with the theory. I cannot help but draw the analogy with small molecule reactions. A kinetic product will be formed first and then converted into the thermodynamic product only if the activation energy for conversion from the kinetic to thermodynamic product is small. Could it be that the proteins that refold meet these criteria? Could it be that they are the exception and not the rule? Obviouslly, this is a simplistic argument, but is it any more simplistic than stating that all proteins fold by the same mechanism? Finally, if proteins do not fold to give a global minimum how can we predict protein folding? Could it be that the generalization is based on hope? I fully expect to be trashed for this opinion, but like all theories only time and experiments will tell. $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ Jeffrey P. Jones Ph.D Assistant Professor of Pharmacology University of Rochester 601 Elmwood Ave. Rochester, NY 14642-8411 (716)275-5371 jpj@lotus.medicine.rochester.edu $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ WE TEND TO MEET ANY NEW SITUATION BY REORGANIZING. IT CAN BE A WONDERFUL METHOD FOR CREATING THE ILLUSION OF PROGRESS WHILE PRODUCING CONFUSION, INEFFICIENCY, AND DEMORALIZATION. -- PETRONIUS ARBITER, 210 B.C. !!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! From JKONG@ac.dal.ca Wed Sep 8 08:35:24 1993 Date: Wed, 08 Sep 1993 11:35:24 -0300 From: JKONG@ac.dal.ca Subject: Q: rs6k fortran buffering To: chemistry@ccl.net Message-Id: <01H2PCIDVQXI00LE25@AC.DAL.CA> Dear netters, The i/o is buffered on rs6k. The problem is you cannot trace the intermediate results, say, in an iteration. Sometimes you want to kill the job if things do not go well. With buffering, you have to wait, which can waste a lot time. Can I get rid of the buffering for a specific unit an output file uses, say 6? Thank you in advance. Jing Kong Dalhousie Univ. Hfx, NS, Canada From mmconn@esau.mit.edu Wed Sep 8 07:45:27 1993 Date: Wed, 8 Sep 93 11:45:27 -0400 From: mmconn@esau.mit.edu (morgan conn) Message-Id: <9309081545.AA21737@esau.mit.edu> To: chemistry@ccl.net Subject: FEP Hello netters, I'm writing this time to find out what people know about public domain packages /programs that can be used for Free Energy Perturbation. The only one that I've seen on the net is MOIL - I was wondering if anybody knew anything else. Thanks, mmc ********************************************************* Morgan Conn MIT Chemistry, 18-148, Cambridge, MA 02139; mmconn@esau.mit.edu, 617.253.6438, 617.253.7929 (fax) ********************************************************* From sliu@mastermodel.ps.uci.edu Wed Sep 8 01:08:10 1993 Message-Id: <9309081608.AA29814@mastermodel.ps.uci.edu> To: chemistry@ccl.net Subject: Definition for .fcm file in CHARMm package Date: Wed, 08 Sep 93 09:08:10 -0800 From: Song Liu Dear Netter : Does anyone know some derail about a file deriv.fcm in CHARMm packages? DX(ATOM) : does it mean dV/dx or -dV/dx and what is the unit for DX ? Thanks! Song Liu Chemistry UC, Irvine From balbes@osiris.rti.org Wed Sep 8 08:41:36 1993 Date: Wed, 8 Sep 93 12:41:36 -0400 From: balbes@osiris.rti.org (Lisa Balbes) Message-Id: <9309081641.AA05818@osiris.rti.org> To: chemistry@ccl.net Subject: Computational Chemistry Yellow Pages In the summary of responses on drug design, my mention of the Computational Chemistry Yellow Pages was listed. Since then I have had several people send me mail and ask me to post info about it. I don't want to get in trouble again, so I'll ask you official opinion. Would it be okay to post the following? In response to several requests, regarding my mention of it, the _Computational Chemistry Yellow Pages_ is a 190 page book published by Molecular Solutions and Custom Research and Consulting. Chapters include: 1. Defining Molecular Modeling 2. Appraoches to Problems 3. Software Vendor Profiles (13 vendors, profile, product & contact info) 4. Software Protocols (software listed by application) 5. Additional Sources (associations, books, consultants, journals, servies, 199 software packages, supercomputer centers and training) 6. Tales from the Bleeding Edge Available for $295 (commercial) or $195(academic) from Molecular Solutions, 412 Carolina Blvd, Isle of Palms, SC, 29451. Phone 803-886-8775 I have no connection with them, other than thinking they wrote a great book. I do not work for them, and they don't pay me money. (Although if they want to, I certainly won't turn it down. Then again, that goes for anyone who wants to give me money.) Lisa % This came directly from a computer and is not to be doubted or disbelieved. % Lisa Balbes Osiris Consultants balbes@osiris.rti.org 2229B Hedgerow Rd, Columbus, OH 43220 614-442-9850 FAX: 614-451-5860 From balbes@osiris.rti.org Wed Sep 8 10:04:18 1993 Date: Wed, 8 Sep 93 14:04:18 -0400 From: balbes@osiris.rti.org (Lisa Balbes) Message-Id: <9309081804.AA06031@osiris.rti.org> To: chemistry@ccl.net Subject: Correction to previous message Please ignore the first paragraph of my previous message. I sent a draft to our (overworked) moderator asking if it would be appropriate to post the information, then forgot to remove it before actually posting. I didn't mean to ask everyone's opinion on its appropriateness, I just need to remember to use my editor. Sorry for the extra bandwidth - Lisa % This came directly from a computer and is not to be doubted or disbelieved. % Lisa Balbes Osiris Consultants balbes@osiris.rti.org 2229B Hedgerow Rd, Columbus, OH 43220 614-442-9850 FAX: 614-451-5860 From mercie@med.cornell.edu Wed Sep 8 09:27:38 1993 Date: Wed, 8 Sep 1993 13:27:38 -0400 (EDT) From: Gustavo Mercier Subject: Re: Natural conformation of protein=global minimum? (fwd) To: chemistry@ccl.net Message-Id: On Thu, 2 Sep 1993, Keith MaloneyHuss x6083 wrote: > Is it assumed that the natural conformation of all proteins is > the free energy global minimum? If so, why? > It must be at least a local minimum, but why assume there is no > possible lower energy state? It is obviously not easily > accessable or it would be the natural configuration. Aren't > there chaperones to assist folding that determine the final conformation, > and thus select conformation based not upon absolute energy minimum criteria > but rather find a good (read very stable) local minimum which is in the > required shape for the protein's function? > This is a chemist/biophysicist answer. Your statement raises the issue of what happens in the cell vs what happens in a test tube and thermodynamic vs kinetic control or a chemical reaction. Experiments in the '60's (Affinsen, I believe) showed the denatured ENZYMES will reconstitute into active forms UNDER THE APPROPRIATE SOLVENT CONDITIONS. The conditions can be very stringent, and many enzymes don't necessarily regain their active form after denaturation, i.e. some denaturing processes are irreversible. Many people failed before he succeeded! Given that at the time all enzymes were proteins (today this is not true!), that the experiments where done in a "test tube", and that proper folding/conformation is necessary for activity, the experiments SUGGESTED that the primary sequence encoded for the active conformation of the enzyme at least in a test tube. Meaning that if you put the primary sequence in the "appropriate solvent" you could get the proper conformers consonant with enzyme activity. As you may expect, the idea was extended to other proteins, even if these were not enzymes. A big deal has been made about how proteins/enzymes achieve the proper conformation in a test tube since simple statistics show that they have too many degrees of freedom to sample the whole phase space in the time that activity is seen to be regained! Therefore, the issues of thermodynamic vs kinetic controlled entered in the process of folding in a test tube. E(denatured/unfolded)+solvent -><- E(renatured/folded)+solvent* under thermodynamic controlled the Free Energy Global Minimum will yield the observed state for the above situation. Under Kinetic Controlled the situation is more complicated and the protein can achieve local minima for a long time. In fact, for MRI contrast agent Gadollinium DTPA is in such a minimum and the chelate is long lived due to Kinetic Control, although the chelate is not in its free energy global minimum. Free Gadolinium is extremely toxic to humans. If thermodynamic control would not exists there would be many deaths from MRI studies with contrast! When moving to the cell the situation is more complicated even before introducing CHAPERONS. Remember the stringent solvent conditions! Now the solvent is much more complex, and the global free energy minimum must account for this! Now, add the chaperons, plus the concepts of thermodynamic vs kinetic control and it is not too far fetched to see the cellular conformation to be very far from the global minimum for the test tube reaction: test tube: see above reaction test tube with chaperon: E(denatured/unfolded) + Chaperon + solvent -><- E(renatured/folded) + Chaperon* + solvent* cell: E(denatured/unfolded)' + Chaperon' + solvent' -><- E(renatured/folded)' + Chaperon'* + solvent'* Notice that for the reaction in the cell I have put primes on E. This is to account for folding as the protein primary sequence is generated in the ribosome. Moreover, the solvent will be different and the Chaperon may have different conformation or, at least, end in a different state given that E is now E'. I hope this shed some light into this discussion. I also hope that I be corrected for any mistakes in the above reasoning! :-) Gus Mercier mercie@cumc.cornell.edu From setlik@acsu.buffalo.edu Wed Sep 8 12:40:30 1993 Date: Wed, 8 Sep 1993 16:40:30 -0400 From: "Robert F. Setlik" Message-Id: <199309082040.QAA05210@lictor.acsu.buffalo.edu> To: CHEMISTRY@ccl.net Subject: protein modeling Does anyone know of a program to create graphic representations of proteins ala Jane Richardson. That is to create cylinder and arrow pictures of protein structures. We need something that is compatable for an E&S or SGI workstation. Thanks, RoB Setlik .. From schurko@CC.UManitoba.CA Wed Sep 8 11:25:49 1993 Date: Wed, 8 Sep 1993 16:25:49 -0500 (CDT) From: Robert Schurko Subject: Re: Units of hyperfine coupling constants To: Jack Houser Message-Id: On Mon, 30 Aug 1993, Jack Houser wrote: > Dear Netters: > > Can anyone tell me what the units are for the hyperfine coupling constants > calculated by the INDO program (QCMP 001)? Are they Hz, Gauss, mT or > something else? I've checked the manual and can't find any discussion of it. > > Thanks. > > Jack Houser Well, since this a fairly old program, and most of Pople's quotes are given in gauss, and the actual formula for the hyperfine coupling constant does not yield Hz, I would strongly assume that the units for these coupling constants are indeed in Gauss. (Definitely not mT! The utilization of this unit by Americans is too new an occurrence in the From schurko@CC.UManitoba.CA Wed Sep 8 11:29:37 1993 Date: Wed, 8 Sep 1993 16:29:37 -0500 (CDT) From: Robert Schurko Subject: Units of hyperfine coupling constants (fwd) To: chemistry@ccl.net Message-Id: > Dear Netters: > > Can anyone tell me what the units are for the hyperfine coupling constants > calculated by the INDO program (QCMP 001)? Are they Hz, Gauss, mT or > something else? I've checked the manual and can't find any discussion of it. > > Thanks. > > Jack Houser Well, since this a fairly old program, and most of Pople's quotes are given in gauss, and the actual formula for the hyperfine coupling constant does not yield Hz, I would strongly assume that the units for these coupling constants are indeed in Gauss. (Definitely not mT! The utilization of this unit by Americans is too new an occurrence in the literature. Rob ============================================================================= schurko@ccu.umanitoba.ca Robert Schurko Chemistry Department (204)-474-9335 University of Manitoba Winnipeg, MB, CANADA ============================================================================= From avs@iris95.biosym.com Wed Sep 8 07:35:32 1993 Message-Id: <9309082135.AA28499@iris95.biosym.com> To: CHEMISTRY@ccl.net Subject: Re: Global min. in protein folding Date: Wed, 08 Sep 93 14:35:32 -0700 From: avs@iris95.biosym.com > Date: Wed, 8 Sep 93 13:12:56 GMT > From: jpj@lotus.medicine.rochester.edu (Jeffrey P. Jones) > Subject: Global min. in protein folding > > While I am not a protein folding person I have conducted an informal poll > of protein folding folks and found that the above generalization is true. > They all site the small proteins that refold as an example. If the protein > cannot be refolded it is an experimental problem since it doesn't agree > with the theory. > I too, am not a protein folding person, and neither am I an experimental chemist. However... IMHO, if the experimental data does not fit the theory, then the problem should be with the theory and not the experimental data. I would think that *any* theory would at the least, try to explain the existing experimental results. **************************************************** Ajay Shah, Ph.D. BIOSYM Technologies avs@biosym.com ****************************************************** Have You Heard of the Symmetry Death of the Universe? ****************************************************** From CHAMANKHAH@sask.usask.ca Wed Sep 8 10:19:38 1993 Date: Wed, 08 Sep 1993 16:19:38 -0600 (CST) From: CHAMANKHAH@sask.usask.ca Subject: Program for Pattern Recognition To: chemistry@ccl.net Message-Id: <01H2PMV2MZW29KM5BL@SKYCAT.USask.CA> Dear netters; Does anyone know if there is any simple and introductory program available on pattern recognition technique used in QSAR studies. We need this program just as a tutorial and our main aim is to find a way to become practically familiar with pattern recognition concepts and application in QSAR. Yours all M.Chamankhah ----------------------------------------------------------------------- From dan@omega.chem.yale.edu Wed Sep 8 14:17:16 1993 From: Dan Severance Message-Id: <9309082217.AA22073@omega.chem.yale.edu> Subject: Re: FEP To: mmconn@esau.mit.edu (morgan conn), chemistry@ccl.net Date: Wed, 8 Sep 93 18:17:16 EDT Organization: Laboratory for Computational Chemistry > > Hello netters, > I'm writing this time to find out what people know about public > domain packages/programs that can be used for Free Energy Perturbation. > The only one that I've seen on the net is MOIL - I was wondering if > anybody knew anything else. > Thanks, > mmc > The BOSS program by Prof. William Jorgensen at Yale (previously at Purdue) is not public domain, but is very inexpensive to academic users. Contact Prof. Jorgensen directly for details: bill@adrik.chem.yale.edu reviews: W.L. Jorgensen, {\it Accounts of Chemical Research}, {\bf 22}, 184 (1989). W.L. Jorgensen, {\it Chemtracts - Organic Chemistry}, {\bf 4}, 91 (1991). (I am a graduate student turned post-doc in his research group) Dan Severance dan@omega.chem.yale.edu From CHAMANKHAH@sask.usask.ca Wed Sep 8 10:28:26 1993 Date: Wed, 08 Sep 1993 16:28:26 -0600 (CST) From: CHAMANKHAH@sask.usask.ca Subject: Training program? To: chemistry@ccl.net Message-Id: <01H2PN5N0UAK9KM5BL@SKYCAT.USask.CA> Dear netters; We are looking for a short term training program including a course and practical sessions in the area of computer aided drug design and QSAR methods using known computer programs. Does anyone out there has some information? We would like to receive responses from both academic and industrial institutions. Thanks for your response.