From owner-chemistry@ccl.net Wed Oct 21 03:32:00 2020 From: "Francois Berenger mlists=-=ligand.eu" To: CCL Subject: CCL: Pharmacophore flexible search tool Message-Id: <-54193-201019211423-19560-rMB+yqMGV6BYrA0SoY1TGA]^[server.ccl.net> X-Original-From: Francois Berenger Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=UTF-8; format=flowed Date: Tue, 20 Oct 2020 10:14:12 +0900 MIME-Version: 1.0 Sent to CCL by: Francois Berenger [mlists-.-ligand.eu] On 19/10/2020 23:10, HOUSTON Douglas DouglasR.Houston|*|ed.ac.uk wrote: > Hi Mark, > > Thanks for your detailed explanation and program suggestions. > > If adding ligand flexibility does not improve the results, then I > guess I don't need it. But I also guess this is dependent on > generating sufficient conformers. How many are sufficient? I realise > this answer will depend on the number of rotatable bonds in each > molecule ... I wrote this Python code using rdkit some time ago: --- # nb. conformers to generate prior to energy minimization # as an empirical function of the molecule's flexibility def how_many_conformers(mol): nb_rot_bonds = AllChem.CalcNumRotatableBonds(mol) if nb_rot_bonds <= 7: return 50 elif nb_rot_bonds <= 12: return 200 return 300 --- The parameters were taken from this publication: "Freely Available Conformer Generation Methods: How Good Are They?" JCIM, 2012, DOI: 10.1021/ci2004658 https://pubs.acs.org/doi/full/10.1021/ci2004658 Regards, F. > Regards, > Doug > > PS I can dock 100,000 molecules into a protein using e.g. PSOVina2 > in a couple of days, and I expect small molecule comparison would go > much faster because the number of grid points would be much lower. > > ------------------------- > > From: owner-chemistry+douglasr.houston==ed.ac.uk-.-ccl.net > on behalf of > Mark Mackey mark_._cresset-group.com > Sent: 15 October 2020 09:41 > To: HOUSTON Douglas > Subject: CCL: Pharmacophore flexible search tool > > Hi Doug, > > The main advantage of pharmacophore methods over more accurate 3D > ligand similarity comparisons is speed: you can preprocess the > database to generate conformations and then searching that database is > extremely fast. Once you allow the method to change conformations you > then have to be able to evaluate the energy of those conformations (or > else it will just find ridiculously high-energy “matches”) and > that is always going to be slow. Docking methods are more-or-less > forced to do this because they generally use very hard van der Waals > interactions with the protein so that if a conformation is a quarter > of an Angstrom out its docking score can increase significantly. > That’s not true for pharmacophore methods, where in general minor > conformation change on a molecule matching the pharmacophore won’t > make it lose the match. > > Even the more accurate 3D ligand similarity methods such as Phase > shape, ROCS or our shape/electrostatic similarity methods in Blaze and > Forge (which, quick plug, are free for graduate students to use!) tend > to rely on precomputed conformations as it is generally significantly > more efficient and adding ligand flexibility does not improve the > results. > > There are exceptions: FlexS from BioSolveIT and the eSim method from > the Jain group both (I believe) incorporate a measure of ligand > flexibility (the latter only for fine-tuning after initially > processing a conformer ensemble), but neither is free as far as I am > aware. > > Is there a reason why you believe you need flexibility during the > match itself? > > Regards, > > Mark > > -- > > Mark Mackey > > Chief Scientific Officer > > Cresset > > New Cambridge House, Bassingbourn Road, Litlington, Cambridgeshire, > SG8 0SS, UK > > tel: +44 (0)1223 858890 mobile: +44 (0)7595 099165 fax: +44 > (0)1223 853667 > > email: mark:+:cresset-group.com web: www.cresset-group.com [1] > skype: mark_cresset > > From: owner-chemistry+mark==cresset-bmd.com:+:ccl.net > On Behalf Of HOUSTON > Douglas DouglasR.Houston[#]ed.ac.uk > Sent: 15 October 2020 07:45 > To: Mark Mackey > Subject: CCL: Pharmacophore flexible search tool > > Hi Sergio, > > Thanks for your reply. Do you know the details of how ZINCPharmer > compares the molecules in the database with the pharmacophore? I note > this from the site: > > "The ZincPharmer search technology uses the Pharmer [2] open source > pharmacophore search technology to efficiently search a large database > of fixed conformers for pharmacophore matches" > > There's a difference between creating a conformer library, and > actually treating each molecule as flexible. > > I already have ways of creating conformer libraries, but what results > is a coarse sampling of all possible conformations. What I'm looking > for is a way of treating the library compounds as actually flexible, > in the same way that e.g. Vina or Autodock treats the small molecule > to be docked into a receptor as flexible. > > Regards, > > Doug > > ------------------------- > > From: owner-chemistry+douglasr.houston==ed.ac.uk-*-ccl.net > on behalf of > Sergio Vechi vechism/agmail.com > Sent: 19 May 2020 21:59 > To: HOUSTON Douglas > Subject: CCL: Pharmacophore flexible search tool > > Dear Doug, > > You can build the pharmacophore model with PharmaGist > (https://bioinfo3d.cs.tau.ac.il/PharmaGist/php.php) and search Zinc > database using ZINCPharmer (http://zincpharmer.csb.pitt.edu/). > > Cheers, > > Sergio > > > +----------------------------------------------------------------------------------------------------------------+ > Dr. Sérgio Vechi | _vechism:gmail.com [3]_ > > Associate Professor > Federal University of Alagoas | Campus Arapiraca | NCEx > > Av. Manuel Severino Barbosa, s/n, Bom Sucesso > > 57309-005 Arapiraca (AL) - Brazil > +----------------------------------------------------------------------------------------------------------------+ > > > On Tue, May 19, 2020 at 4:35 PM HOUSTON Douglas > DouglasR.Houston]![ed.ac.uk [4] wrote: > >> Hi all, >> >> Does anyone know of a free (for academics at least) chemical search >> tool, that will screen a large compound library (say an SDF of >> 100,000 molecules) against a reference pharmacophore/ligand, and >> treat the library compounds as flexible and not rigid? >> >> I've asked this before but for some reason the formatting was so >> screwed up I don't think most people could read it! >> >> Regards, >> >> Doug >> >> > ------------------------------------------------------------------------------------------ >> >> >> Dr. Douglas R. Houston >> >> Senior Lecturer in Computational Biochemistry >> >> Institute of Quantitative Biology, Biochemistry and Biotechnology >> >> Room 2.12, Waddington 1 Building >> >> King's Buildings >> >> University of Edinburgh >> >> Edinburgh, EH9 3BF, UK >> >> Tel. 07986875743 >> >> The University of Edinburgh is a charitable body, registered in >> Scotland, with registration number SC005336. > > > Links: > ------ > [1] http://www.cresset-group.com/ > [2] http://smoothdock.ccbb.pitt.edu/pharmer/ > [3] http://gmail.com > [4] http://ed.ac.uk From owner-chemistry@ccl.net Wed Oct 21 04:07:00 2020 From: "HOUSTON Douglas DouglasR.Houston*_*ed.ac.uk" To: CCL Subject: CCL: Pharmacophore flexible search tool Message-Id: <-54194-201021030825-1229-6oyHTGRp+BE7oH3ZVrjbJw{=}server.ccl.net> X-Original-From: HOUSTON Douglas Content-Language: en-GB Content-Type: multipart/alternative; boundary="_000_DBAPR05MB7047DAEBB0916E7A8EF12307A81C0DBAPR05MB7047eurp_" Date: Wed, 21 Oct 2020 07:08:12 +0000 MIME-Version: 1.0 Sent to CCL by: HOUSTON Douglas [DouglasR.Houston- -ed.ac.uk] --_000_DBAPR05MB7047DAEBB0916E7A8EF12307A81C0DBAPR05MB7047eurp_ Content-Type: text/plain; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Hi Mark, Many thanks, that's very helpful. Best regards, Doug ________________________________ > From: owner-chemistry+douglasr.houston=3D=3Ded.ac.uk~~ccl.net on behalf of Mark Mackey mark ..= cresset-group.com Sent: 19 October 2020 19:52 To: HOUSTON Douglas Subject: CCL: Pharmacophore flexible search tool Hi Doug, There are a number of papers in the literature that suggest that you only n= eed surprisingly few conformations (eg https://link.springer.com/article/10= .1007%2Fs10822-014-9813-4). The argument is that as you increase the covera= ge of conformation space you make it more likely that you=92ll pick up a tr= ue positive, but you also make it more likely that a false positive will gi= ve a good score, so overall your hit rate doesn=92t improve. I think that t= here=92s definitely something to that claim, but I would argue that the thr= eshold of 10 confs or so that people tend to suggest is too low and the stu= dies showing that this is sufficient are likely to be biased by all of the = well-known problems with retrospective virtual screening experiments (see h= ttps://www.cresset-group.com/about/news/virtual-screening-how-many-conforma= tions-is-enough/). All of this is assuming that your compounds fall into the small-molecule-dr= uglike category, with a reasonable molecular weight and <10 rotatable bonds= . Within these constraints, 100 confs from a decent conformer generator is = probably describing the conformation space pretty well: our conformation hu= nter will get virtually all compounds with 6-7 rotatable bonds right (in th= e sense of having a conformation within 1-1.5A RMSD off the bioactive confo= rmation) with a 100 conf limit. That does fall off fairly quickly with flex= ibility, though: at 9-10 rotatable bonds you=92re looking at 50/50 whether = you=92ll find something close to the bioactive conf, and once you=92re much= above that the success rate drops off a cliff. Other conf hunt methods get= similar performance. If you are actually interested in a bunch of decapeptides or similar then i= t=92s basically impossible to pre-enumerate or describe the conformation sp= ace. In that case some sort of flexible fit algorithm may be your only chan= ce of getting a sensible result. The caveat, of course, is that the average= decapeptide is going to match every single pharmacophore model you can thi= nk of=85 The other problem with flexible fitting is accounting for the relative conf= ormation energy of the ligand (which is a much more complicated question th= an it sounds, but that=92s another post). If you pre-enumerate you can comp= are energies for each conformer to the energy of the =93best=94 one that yo= u found and filter out the high-energy ones. With a flexible alignment you = do need to account for conformer energy (otherwise you=92ll just bend the m= olecule into a dumb conformation to make it fit the pharmacophore), but you= don=92t have a known reference low-energy conformation to compare to so yo= u won=92t know if your fitted ensemble are energetically reasonable or not.= There are ways around that, but they aren=92t as rigorous. You are right that flexible fitting of ~100K mols to a pharmacophore or sha= pe model is perfectly doable in a few CPU days. Most pharmacophore software= has been designed with the aim of screening millions of molecules in a few= hours, however, which is why they tend to use pre-enumerated conformations= . Regards, Mark -- Mark Mackey Chief Scientific Officer Cresset New Cambridge House, Bassingbourn Road, Litlington, Cambridgeshire, SG8 0SS= , UK tel: +44 (0)1223 858890 mobile: +44 (0)7595 099165 fax: +44 (0)1223 8= 53667 email: mark : cresset-group.com web= : www.cresset-group.com skype: mark_cress= et > From: owner-chemistry+mark=3D=3Dcresset-bmd.com : ccl.net On Behalf Of HOUSTON Douglas DouglasR.= Houston|*|ed.ac.uk Sent: 19 October 2020 15:11 To: Mark Mackey Subject: CCL: Pharmacophore flexible search tool Hi Mark, Thanks for your detailed explanation and program suggestions. If adding ligand flexibility does not improve the results, then I guess I d= on't need it. But I also guess this is dependent on generating sufficient c= onformers. How many are sufficient? I realise this answer will depend on th= e number of rotatable bonds in each molecule ... Regards, Doug PS I can dock 100,000 molecules into a protein using e.g. PSOVina2 in a co= uple of days, and I expect small molecule comparison would go much faster b= ecause the number of grid points would be much lower. ________________________________ > From: owner-chemistry+douglasr.houston=3D=3Ded.ac.uk-.-ccl.net on behalf of Mark Mackey mar= k_._cresset-group.com Sent: 15 October 2020 09:41 To: HOUSTON Douglas Subject: CCL: Pharmacophore flexible search tool Hi Doug, The main advantage of pharmacophore methods over more accurate 3D ligand si= milarity comparisons is speed: you can preprocess the database to generate = conformations and then searching that database is extremely fast. Once you = allow the method to change conformations you then have to be able to evalua= te the energy of those conformations (or else it will just find ridiculousl= y high-energy =93matches=94) and that is always going to be slow. Docking m= ethods are more-or-less forced to do this because they generally use very h= ard van der Waals interactions with the protein so that if a conformation i= s a quarter of an Angstrom out its docking score can increase significantly= . That=92s not true for pharmacophore methods, where in general minor confo= rmation change on a molecule matching the pharmacophore won=92t make it los= e the match. Even the more accurate 3D ligand similarity methods such as Phase shape, RO= CS or our shape/electrostatic similarity methods in Blaze and Forge (which,= quick plug, are free for graduate students to use!) tend to rely on precom= puted conformations as it is generally significantly more efficient and add= ing ligand flexibility does not improve the results. There are exceptions: FlexS from BioSolveIT and the eSim method from the Ja= in group both (I believe) incorporate a measure of ligand flexibility (the = latter only for fine-tuning after initially processing a conformer ensemble= ), but neither is free as far as I am aware. Is there a reason why you believe you need flexibility during the match its= elf? Regards, Mark -- Mark Mackey Chief Scientific Officer Cresset New Cambridge House, Bassingbourn Road, Litlington, Cambridgeshire, SG8 0SS= , UK tel: +44 (0)1223 858890 mobile: +44 (0)7595 099165 fax: +44 (0)1223 8= 53667 email: mark:+:cresset-group.com web: ww= w.cresset-group.com skype: mark_cresset > From: owner-chemistry+mark=3D=3Dcresset-bmd.com:+:ccl.net On Behalf Of HOUSTON Douglas DouglasR.= Houston[#]ed.ac.uk Sent: 15 October 2020 07:45 To: Mark Mackey Subject: CCL: Pharmacophore flexible search tool Hi Sergio, Thanks for your reply. Do you know the details of how ZINCPharmer compares = the molecules in the database with the pharmacophore? I note this from the = site: "The ZincPharmer search technology uses the Pharmer open source pharmacophore search technology to efficient= ly search a large database of fixed conformers for pharmacophore matches" There's a difference between creating a conformer library, and actually tre= ating each molecule as flexible. I already have ways of creating conformer libraries, but what results is a = coarse sampling of all possible conformations. What I'm looking for is a wa= y of treating the library compounds as actually flexible, in the same way t= hat e.g. Vina or Autodock treats the small molecule to be docked into a rec= eptor as flexible. Regards, Doug ________________________________ > From: owner-chemistry+douglasr.houston=3D=3Ded.ac.uk-*-ccl.net on behalf of Sergio Vechi ve= chism/agmail.com Sent: 19 May 2020 21:59 To: HOUSTON Douglas Subject: CCL: Pharmacophore flexible search tool Dear Doug, You can build the pharmacophore model with PharmaGist (https://bioinfo3d.cs= .tau.ac.il/PharmaGist/php.php) and search Zinc database using ZINCPharmer (= http://zincpharmer.csb.pitt.edu/). Cheers, Sergio +--------------------------------------------------------------------------= --------------------------------------+ Dr. S=E9rgio Vechi | vechism:gmail.com Associate Professor Federal University of Alagoas | Campus Arapiraca | NCEx Av. Manuel Severino Barbosa, s/n, Bom Sucesso 57309-005 Arapiraca (AL) - Brazil +--------------------------------------------------------------------------= --------------------------------------+ On Tue, May 19, 2020 at 4:35 PM HOUSTON Douglas DouglasR.Houston]![ed.ac.uk= > wrote: Hi all, Does anyone know of a free (for academics at least) chemical search tool, t= hat will screen a large compound library (say an SDF of 100,000 molecules) = against a reference pharmacophore/ligand, and treat the library compounds a= s flexible and not rigid? I've asked this before but for some reason the formatting was so screwed up= I don't think most people could read it! Regards, Doug ---------------------------------------------------------------------------= --------------- Dr. Douglas R. Houston Senior Lecturer in Computational Biochemistry Institute of Quantitative Biology, Biochemistry and Biotechnology Room 2.12, Waddington 1 Building King's Buildings University of Edinburgh Edinburgh, EH9 3BF, UK Tel. 07986875743 The University of Edinburgh is a charitable body, registered in Scotland, w= ith registration number SC005336. --_000_DBAPR05MB7047DAEBB0916E7A8EF12307A81C0DBAPR05MB7047eurp_ Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable
Hi Mark,

Many thanks, that's very helpful.

Best regards,
Doug


From: owner-chemistry+dougl= asr.houston=3D=3Ded.ac.uk~~ccl.net <owner-chemistry+douglasr.houston=3D= =3Ded.ac.uk~~ccl.net> on behalf of Mark Mackey mark .. cresset-group.com <owner-chemistry~~ccl.net>
Sent: 19 October 2020 19:52
To: HOUSTON Douglas <DouglasR.Houston~~ed.ac.uk>
Subject: CCL: Pharmacophore flexible search tool
 

Hi Doug,

 

There are a number of papers in the literature that sugges= t that you only need surprisingly few conformations (eg h= ttps://link.springer.com/article/10.1007%2Fs10822-014-9813-4). The argu= ment is that as you increase the coverage of conformation space you make it= more likely that you=92ll pick up a true positive, but you also make it more likely that a false positive will= give a good score, so overall your hit rate doesn=92t improve. I think tha= t there=92s definitely something to that claim, but I would argue that the = threshold of 10 confs or so that people tend to suggest is too low and the studies showing that this is sufficient= are likely to be biased by all of the well-known problems with retrospecti= ve virtual screening experiments (see https://www.cresset-group.com/about/news/virtual-screening-how-many-conform= ations-is-enough/).

 

All of this is assuming that your compounds fall into the = small-molecule-druglike category, with a reasonable molecular weight and &l= t;10 rotatable bonds. Within these constraints, 100 confs from a decent con= former generator is probably describing the conformation space pretty well: our conformation hunter will get virtu= ally all compounds with 6-7 rotatable bonds right (in the sense of having a= conformation within 1-1.5A RMSD off the bioactive conformation) with a 100= conf limit. That does fall off fairly quickly with flexibility, though: at 9-10 rotatable bonds you=92re = looking at 50/50 whether you=92ll find something close to the bioactive con= f, and once you=92re much above that the success rate drops off a cliff. Ot= her conf hunt methods get similar performance.

 

If you are actually interested in a bunch of decapeptides = or similar then it=92s basically impossible to pre-enumerate or describe th= e conformation space. In that case some sort of flexible fit algorithm may = be your only chance of getting a sensible result. The caveat, of course, is that the average decapeptide is going to= match every single pharmacophore model you can think of=85

 

The other problem with flexible fitting is accounting for = the relative conformation energy of the ligand (which is a much more compli= cated question than it sounds, but that=92s another post). If you pre-enume= rate you can compare energies for each conformer to the energy of the =93best=94 one that you found and filter ou= t the high-energy ones. With a flexible alignment you do need to account fo= r conformer energy (otherwise you=92ll just bend the molecule into a dumb c= onformation to make it fit the pharmacophore), but you don=92t have a known reference low-energy conformation to compare = to so you won=92t know if your fitted ensemble are energetically reasonable= or not. There are ways around that, but they aren=92t as rigorous.<= /p>

 

You are right that flexible fitting of ~100K mols to a pha= rmacophore or shape model is perfectly doable in a few CPU days. Most pharm= acophore software has been designed with the aim of screening millions of m= olecules in a few hours, however, which is why they tend to use pre-enumerated conformations.

 

Regards,

Mark

 

-- =

Mark Macke= y

Chief Scie= ntific Officer

Cresset

New Cambridge= House, Bassingbourn Road, Litlington, Cambridgeshire, SG8 0SS, UK

tel: +44 (0)1= 223 858890    mobile: +44 (0)7595 099165  &nb= sp; fax: +44 (0)1223 853667

email:= mark : = cresset-group.com    web: www.cresset-group.com&= nbsp;   skype: mark_cresset

 

 

 

From: owner-chemist= ry+mark=3D=3Dcresset-bmd.com : ccl.net <owner-chemistry+mark=3D=3Dcresse= t-bmd.com : ccl.net> On Behalf Of HOUSTON Douglas DouglasR.Houston|*|ed.ac.uk
Sent: 19 October 2020 15:11
To: Mark Mackey <mark : cresset-group.com>
Subject: CCL: Pharmacophore flexible search tool

 

Hi Mark,

 

Thanks for your detailed expl= anation and program suggestions.

 

If adding ligand flexibi= lity does not improve the results, then I guess I don't need it. But I also= guess this is dependent on generating sufficient conformers. How many are = sufficient? I realise this answer will depend on the number of rotatable bonds in each molecule ...

 

Regards,

Doug

 

PS  I can dock 100,000 m= olecules into a protein using e.g. PSOVina2 in a couple of days, and I expe= ct small molecule comparison would go much faster because the number of gri= d points would be much lower.

 

From:= owner-chemistry+douglasr.houston=3D=3Ded.ac.uk-.-ccl.net <owner-chemist= ry+douglasr.houston=3D=3Ded.ac.uk-.-ccl.net> on behalf of Mark Mackey ma= rk_._cresset-group.com <owner-chemistry-.-ccl.net>
Sent: 15 October 2020 09:41
To: HOUSTON Douglas <DouglasR.Houston-.-ed.ac.uk>
Subject: CCL: Pharmacophore flexible search tool

 

Hi Doug,

 

The main advantage of pharmacophore methods over more accurate 3D ligand si= milarity comparisons is speed: you can preprocess the database to generate = conformations and then searching that database is extremely fast. Once you = allow the method to change conformations you then have to be able to evaluate the energy of those conformations (or= else it will just find ridiculously high-energy =93matches=94) and that is= always going to be slow. Docking methods are more-or-less forced to do thi= s because they generally use very hard van der Waals interactions with the protein so that if a conformation is a= quarter of an Angstrom out its docking score can increase significantly. T= hat=92s not true for pharmacophore methods, where in general minor conforma= tion change on a molecule matching the pharmacophore won=92t make it lose the match.

 

Even the more accurate 3D ligand similarity methods such as Phase shape, RO= CS or our shape/electrostatic similarity methods in Blaze and Forge (which,= quick plug, are free for graduate students to use!) tend to rely on precom= puted conformations as it is generally significantly more efficient and adding ligand flexibility does not improv= e the results.

 

There are exceptions: FlexS from BioSolveIT and the eSim method from the Ja= in group both (I believe) incorporate a measure of ligand flexibility (the = latter only for fine-tuning after initially processing a conformer ensemble= ), but neither is free as far as I am aware.

 

Is there a reason why you believe you need flexibility during the match its= elf?

 

Regards,

Mark

 

-- =

Mark Macke= y

Chief Scie= ntific Officer

Cresset

New Cambridge= House, Bassingbourn Road, Litlington, Cambridgeshire, SG8 0SS, UK

tel: +44 (0)1= 223 858890    mobile: +44 (0)7595 099165  &nb= sp; fax: +44 (0)1223 853667

email:= mark:+:= cresset-group.com    web: www.cresset-group.com&= nbsp;   skype: mark_cresset

 

 

 

From: owner-chemist= ry+mark=3D=3Dcresset-bmd.com:+:ccl.net <owner-chemistry+mark=3D=3Dcresse= t-bmd.com:+:ccl.net> On Behalf Of HOUSTON Douglas DouglasR.Houston[#]ed.ac.uk
Sent: 15 October 2020 07:45
To: Mark Mackey <mark:+:cresset-group.com>
Subject: CCL: Pharmacophore flexible search tool

 

Hi Sergio,

 

Thanks for your reply. Do you= know the details of how ZINCPharmer compares the molecules in the database= with the pharmacophore? I note this from the site:

 

"The ZincPharmer search technology uses the Pharmer open source pharmacophore search technology to efficiently search a large datab= ase of fixed conformers for pharmacophore matches"

 

There's a d= ifference between creating a conformer library, and actually treating each = molecule as flexible.

 

I already h= ave ways of creating conformer libraries, but what results is a coarse samp= ling of all possible conformations. What I'm looking for is a way of treati= ng the library compounds as actually flexible, in the same way that e.g. Vina or Autodock treats= the small molecule to be docked into a receptor as flexible.

 

Regards,

Doug=

 

 

From:= owner-chemistry+douglasr.houston=3D=3Ded.ac.uk-*-ccl.net <owner-chemist= ry+douglasr.houston=3D=3Ded.ac.uk-*-ccl.net> on behalf of Sergio Vechi v= echism/agmail.com <owner-chemistry-*-ccl.net>
Sent: 19 May 2020 21:59
To: HOUSTON Douglas <DouglasR.Houston-*-ed.ac.uk>
Subject: CCL: Pharmacophore flexible search tool

 

Dear Doug,

 

You can build the pharm= acophore model with PharmaGist (https://bioinfo3d.cs.tau.ac.il/PharmaGist/php.php) a= nd search Zinc database using ZINCPharmer (http://zincpharmer.csb.pitt.edu/).

 

Cheers,

 

Sergio

+----------------------------------------------= ------------------------------------------------------------------+
   Dr. S=E9rgio Vechi | vechism:gmail.com           =                     &nbs= p;  
     Associate Professor
     Federal University of Alagoas | Campus Arapiraca |= NCEx

     Av. Manuel Severino Barbosa= , s/n, Bom Sucesso

     57309-005 Arapiraca (A= L) - Brazil                  &= nbsp;     
+--------------------------------------------------------------------------= --------------------------------------+

 

 

On Tue, May 19, 2020 at 4:35 PM HOUSTON Douglas DouglasR.Houston]![ed.ac.uk <owner-chemistry|,|ccl.net> wrote:

Hi all,

 

Does anyone know of a free (for academics at l= east) chemical search tool, that will screen a large compound lib= rary (say an SDF of 100,000 molecules) against a reference pharmacophore/ligand, and treat the library compounds as flexible and not = rigid?

 

I've asked this before but for some reason the= formatting was so screwed up I don't think most people could read it!

 

Regards,

Doug

 

----------------------------------------------= --------------------------------------------

Dr. Douglas= R. Houston

Senior Lect= urer in Computational Biochemistry

Institute o= f Quantitative Biology, Biochemistry and Biotechnology

Room 2.12,&= nbsp;Waddington 1 Building

King's Buil= dings

University = of Edinburgh

Edinburgh,&= nbsp;EH9 3BF, UK

Tel. 079868= 75743

 

The University of Edinburgh is a charitable body, registered in Scotland, w= ith registration number SC005336.

--_000_DBAPR05MB7047DAEBB0916E7A8EF12307A81C0DBAPR05MB7047eurp_--