From owner-chemistry@ccl.net Fri Jul 11 03:16:01 2008 From: "Vidana.Epa .. csiro.au" To: CCL Subject: CCL: Protein-Ligand CONSTRAINED Docking Message-Id: <-37324-080711005948-12951-NTUNpc5PjXoJlHlL7cdmaA!^!server.ccl.net> X-Original-From: Content-Class: urn:content-classes:message Content-Transfer-Encoding: quoted-printable Content-Type: text/plain; charset="US-ASCII" Date: Fri, 11 Jul 2008 14:23:51 +1000 MIME-Version: 1.0 Sent to CCL by: [Vidana.Epa^csiro.au] Hi Richard, Doesn't the "-fmatch" option of Surflex-Dock (constraining the docking to a pre-placed fragment) do what you need to achieve? I am also curious as to why you came to the conclusion that Glide is not up to your standards. Cheers, Vidana. Vidana C. Epa =20 CSIRO, Division of Molecular Health & Technologies, 343 Royal Parade, Parkville, Victoria 3052, AUSTRALIA. =20 tel: (61) - 3 - 9662 - 7345 fax:(61) - 3 - 9662 - 7347 =20 email: Vidana.Epa++csiro.au -----Original Message----- > From: owner-chemistry++ccl.net [mailto:owner-chemistry++ccl.net]=20 Sent: Friday, 11 July 2008 8:07 AM To: Epa, Vidana (CMHT, Parkville) Subject: CCL: Protein-Ligand CONSTRAINED Docking Sent to CCL by: "Richard Wood" [rwoodphd##msn.com] Hi all, I have a series of ligands which I've docked to a protein using=20 Surflex-Dock as implemented in Sybyl. Unfortunately, my results don't explain some experimental observations=20 so I would like to do some contrained docking. I've been looking into FlexX-Pharm, but it seems to only allow one to constrain an ELEMENT of the ligand to be a certain radius from a certain atom (which one can choose) in the protein target. For example, one can pick a nitrogen in a ligand to be within a 3.0 Angstrom radius of a given protein atom, say. This is problematic if your ligand has several nitrogens or carbons in=20 them, as one cannot pick atom types or atom numbers. I'm wondering if=20 there is a workaround to this; I'd like to stay with Sybyl as my boss=20 wants me to use it, and we've decided Glide is not up to our standards.=20 To conclude, I would like to be able to pick a particular ligand atom and constrain it to be a certain distance from a protein atom, that I again pick, and then dock it. As it stands now, I can only constrain a (any) nitrogen in my ligand (I think the fact that my ligand is not introduced at any point, prior to docking, into this process is what is problematic) to be within a radius of a protein atom, and not a fixed distance. Basically, I want to constrain an imidazole nitrogen (say) to be 2.4 Angstroms away from an iron atom in a heme group, or a methyl group to be 3.0 Angstroms from the same atom, and not WITHIN a radius of this distance, since it can be anywhere from 0 to the distance I want, and lead to situations I'm seeing now, where the molecule I'm docking is on top of the heme. TIA, Richard -=3D This is automatically added to each message by the mailing script = =3D-http://www.ccl.net/cgi-bin/ccl/send_ccl_messageSubscribe/Unsubscribe:=20Job: http://www.ccl.net/jobs=20http://www.ccl.net/spammers.txt From owner-chemistry@ccl.net Fri Jul 11 08:14:01 2008 From: "Nicola Zonta zontan]=[cf.ac.uk" To: CCL Subject: CCL: Zodiac release Message-Id: <-37325-080711071649-2415-o6y9jcC1sMRAo7EVtgSwXA**server.ccl.net> X-Original-From: "Nicola Zonta" Date: Fri, 11 Jul 2008 07:16:45 -0400 Sent to CCL by: "Nicola Zonta" [zontan^^^cf.ac.uk] Dear CCLers, I would like to announce the release of Zodiac, a software for molecular modelling - computer-aided drug design. Complete information and download links can be found at www.zeden.org. Here are some links to OS-specific executables: Windows: http://www.softpedia.com/get/Science-CAD/Zodiac.shtml MacOsX: http://mac.softpedia.com/get/Math-Scientific/Zodiac.shtml Linux : http://linux.softpedia.com/get/Utilities/Zodiac-37209.shtml Zodiac is an open-source project hosted on sourceforge http://sourceforge.net/projects/zodiac-zeden/ As with every open-source project, I strongly encourage any kind of feedback, such as bug reports, screenshots, contributions to the developement, collaborations with other (GPL) projects. Any comment is warmly welcome! Nicola Zonta From owner-chemistry@ccl.net Fri Jul 11 08:52:01 2008 From: "Zhao Yuan ccl+/-mail.sioc.ac.cn" To: CCL Subject: CCL: questions about ECFPs Message-Id: <-37326-080711085003-24201-P/1t6ITFX5s2wxuCNkbUoQ^server.ccl.net> X-Original-From: "Zhao Yuan" Date: Fri, 11 Jul 2008 08:50:00 -0400 Sent to CCL by: "Zhao Yuan" [ccl]~[mail.sioc.ac.cn] Hi everyone, Recently, I've read the paper about how to generate Extended-Connectivity Fingerprints. ///////////////////////////////////////////// High-Throughput Data Analysis. 1. Extended-Connectivity Fingerprints: A High-Dimensional Descriptor for Molecular Data Analysis David Rogers* and Mathew Hahn SciTegic, Inc. ///////////////////////////////////////////// It mentioned that ECFPs can be rapidly calculated and can represent a very large number of different features. So I want to use it to compare two molecules or calculate similarity between them. However, I met some detailed and technical problem when following its method. The first problem is the hash function. I used lots of hash function to encode the initial atom identifiers but none of them is identical to the result in the reference. Does anyone know what hash function it used? Second, after the first iteration, the code of root atom's neighbors are attached to the code of root atom. Then it got a array like this: [1, 3194967052, 1, 1559650422, 1, 1572579716, 2, 3220825640] I wondered whether it needed to sort again. (in my program, the array was like this: 13194967052, 11559650422, 11572579716, 23220825640 then I converted them to a sorted or unsorted string which will be used for hash function. sorted string: 11559650422115725797161319496705223220825640 unsorted string: 13194967052115596504221157257971623220825640 but whatever string I used, the new features I got was different > from the reference result. Third, for the second iteration, some atoms may connect to the same neighboring atoms. Such as in a four membered ring, B and C are the neighbor of atom A, while D connected to B and C. In the second iteration, which atom should the D's code attach (B or C or Both)? A----B | | C----D At last, can anybody give me a detailed example of the ECFPs_4. The initial identifier of each atom and the identifiers in each iterations ( identifier before hash and after hash ). I've tried to correspond with the author Dr. Rogers, however his e-mail is not valid now. I sincerely appreciate if anyone can give me some help in resolving the problem. Best Regards, Zhao Yuan ------------------------------------------------------------ State Key Lab of Bio-organic and Natural Products Chemistry Shanghai Institute of Organic Chemistry (SIOC), Chinese Academy of Sciences. Addr. 354, Fenglin Road, Shanghai, China. Tel.: +86-21-54925275 Email: yzhao.^.mail.sioc.ac.cn From owner-chemistry@ccl.net Fri Jul 11 10:59:00 2008 From: "Willy Offermans Willy~~Offermans.Rompen.nl" To: CCL Subject: CCL: Solubility in polymers Message-Id: <-37327-080711092507-16109-tj+775NnS7/RvPy7U9iqNg.:.server.ccl.net> X-Original-From: Willy Offermans Content-Disposition: inline Content-Transfer-Encoding: 8bit Content-Type: text/plain; charset=iso-8859-1 Date: Fri, 11 Jul 2008 14:53:10 +0200 MIME-Version: 1.0 Sent to CCL by: Willy Offermans [Willy*o*Offermans.Rompen.nl] Dear CCL friends, I like to investigate the solubility of small molecules in polymers computationally. Can you advice me how to proceed or point me to some literature or other sources to start with? -- Met vriendelijke groeten, With kind regards, Mit freundlichen Gruessen, De jrus wah, Willy ************************************* Dr. W.K. Offermans CAT Postdoctoral Fellow CAT Catalytic Center Institut für Technische und Makromolekulare Chemie RWTH Aachen Worringerweg 1, Raum 38C-150 D-52074 Aachen, Germany Phone: +49 241 80 28592 Home: +31 45 544 49 44 Mobile: +31 653 27 16 23 e-mail: Willy|,|Offermans.Rompen.nl e-mail: Willy.Offermans|,|CatalyticCenter.RWTH-Aachen.de Powered by .... (__) \\\'',) \/ \ ^ .\._/_) www.FreeBSD.org From owner-chemistry@ccl.net Fri Jul 11 11:43:01 2008 From: "Iain Wallace iain.m.wallace * gmail.com" To: CCL Subject: CCL: Estimating applicability of fingerprint model Message-Id: <-37328-080711114039-5883-pH1IHqHGl2bNIq4kwaWcgw(!)server.ccl.net> X-Original-From: "Iain Wallace" Content-Type: multipart/alternative; boundary="----=_Part_29212_610929.1215790402926" Date: Fri, 11 Jul 2008 11:33:22 -0400 MIME-Version: 1.0 Sent to CCL by: "Iain Wallace" [iain.m.wallace!^!gmail.com] ------=_Part_29212_610929.1215790402926 Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline Hi all, I have built a model to classify compounds into two classes using the Pipeline pilot Bayesian fingerprint classifier (ECFP_4 Fingerprints). I was wondering if anyone has any experience on how to estimate how well the model I have built will transfer to other libraries? I know that I should only apply the model to compounds drawn from a similar distribution, but I have no idea how to what steps I should take to ensure that this criteria is met. For instance, I would like to score the Zinc database (all commercially available compounds) to find new interesting molecules, and I am wondering if anyone has any tips on problems I should look out for, Thanks for alot for any advice Iain ------=_Part_29212_610929.1215790402926 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline Hi all,

I have built a model to classify compounds into two classes using the Pipeline pilot Bayesian fingerprint classifier (ECFP_4 Fingerprints).   I was wondering if anyone has any experience on how to estimate how well the model I have built will transfer to other libraries? I know that I should only apply the model to compounds drawn from a similar distribution, but I have no idea how to what steps I should take to ensure that this criteria is met.

For instance, I would like to score the Zinc database (all commercially available compounds) to find new interesting molecules, and I am wondering if anyone has any tips on problems I should look out for,

Thanks for alot for any advice

Iain

------=_Part_29212_610929.1215790402926-- From owner-chemistry@ccl.net Fri Jul 11 13:14:01 2008 From: "Rajarshi Guha rguha]=[indiana.edu" To: CCL Subject: CCL: Estimating applicability of fingerprint model Message-Id: <-37329-080711131050-13382-9D/I3oFj3niYCMV93Z1Luw##server.ccl.net> X-Original-From: Rajarshi Guha Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=US-ASCII; delsp=yes; format=flowed Date: Fri, 11 Jul 2008 12:22:50 -0400 Mime-Version: 1.0 (Apple Message framework v753.1) Sent to CCL by: Rajarshi Guha [rguha- -indiana.edu] -----BEGIN PGP SIGNED MESSAGE----- Hash: SHA1 On Jul 11, 2008, at 11:33 AM, Iain Wallace iain.m.wallace * gmail.com wrote: > Hi all, > > I have built a model to classify compounds into two classes using > the Pipeline pilot Bayesian fingerprint classifier (ECFP_4 > Fingerprints). I was wondering if anyone has any experience on > how to estimate how well the model I have built will transfer to > other libraries? I know that I should only apply the model to > compounds drawn from a similar distribution, but I have no idea how > to what steps I should take to ensure that this criteria is met. A relatively simple approach is to use the method described in JCAMD, 2008, 22, 367-384 (http://dx.doi.org/10.1007/s10822-008-9192-9) - ------------------------------------------------------------------- Rajarshi Guha GPG Fingerprint: D070 5427 CC5B 7938 929C DD13 66A1 922C 51E7 9E84 - ------------------------------------------------------------------- Brain fried -- Core dumped -----BEGIN PGP SIGNATURE----- Version: GnuPG v1.4.8 (Darwin) iEYEARECAAYFAkh3iNoACgkQZqGSLFHnnoSpXACeI62eKO/AP3HSGuogUC+50xYb jrUAn2nM0c0rDcCV2vsTDFdsjGmO3Iz5 =RzlN -----END PGP SIGNATURE----- From owner-chemistry@ccl.net Fri Jul 11 14:29:00 2008 From: "Jim Kress ccl_nospam^^kressworks.com" To: CCL Subject: CCL: instal Message-Id: <-37330-080709105720-371-bUD/UDsjEOnS3wlj/oC4ew]*[server.ccl.net> X-Original-From: "Jim Kress" Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset="us-ascii" Date: Wed, 9 Jul 2008 10:46:30 -0400 MIME-Version: 1.0 Sent to CCL by: "Jim Kress" [ccl_nospam[A]kressworks.com] Gromacs (http://www.gromacs.org) Tinker (http://dasher.wustl.edu/tinker/) And, of course, you could try googling "molecular modeling software" and get a really long list. > -----Original Message----- > From: owner-chemistry++ccl.net [mailto:owner-chemistry++ccl.net] > Sent: Monday, July 07, 2008 4:49 PM > To: Kress, Jim > Subject: CCL: instal > > > Sent to CCL by: "nee mis" [neerajmisra|a|hotmail.com] > I am looking for a free program used for molecular > modeling of large organic or biological molecules which can > include three-body and four-body interactions. I shall be > thankful for the suggestions. > > > > -= This is automatically added to each message by the mailing > script =- To recover the email address of the author of the > message, please change the strange characters on the top line > to the ++ sign. You can also look up the X-Original-From: line > in the mail header.> Conferences: > http://server.ccl.net/chemistry/announcements/conferences/ > > Search Messages: http://www.ccl.net/htdig (login: ccl, > Password: search)> > From owner-chemistry@ccl.net Fri Jul 11 19:29:00 2008 From: "Marcus Gastreich support%biosolveit.de" To: CCL Subject: CCL: Protein-Ligand CONSTRAINED Docking Message-Id: <-37331-080711115119-13352-1/MK9Bzqoyb/7MwU6CsAjw**server.ccl.net> X-Original-From: "Marcus Gastreich" Date: Fri, 11 Jul 2008 11:51:15 -0400 Sent to CCL by: "Marcus Gastreich" [support,,biosolveit.de] hello richard- thanks for asking - i am confident that flexx 3.* with its own GUI will be very much up to your standards. ;-) it's freely downloadable from www.biosolveit.de/download and will check out a license only once you press "Apply & Dock!". in flexx-pharm, there are some ways to achieve what you want a) you can constrain a SMARTS subgraph expression in such a way that only one specific nitrogen will match the expression and thus be allowed to be placed in a very "spatial constraint" (i.e., the sphere you define). so, the spatial definition possibilities go beyond the pure "element". multiple, overlapping spheres should give you the freedom to play with as many distances as you require. b) there is a biosolveit extension to smarts implemented which allows you to use sybyl atom typing in smarts. it uses curly braces, e.g., [{C.2}] c) place manually, then grow. in flexx's core facility there is the possibility of placing one part of your molecule and then let the rest grow automatically. this can, e.g., be used for docking families of compounds which share a common part which places in a similar way. but here, you could use the mechanism to place an imiadzole just in the way you like, then let flexx/-pharm do the rest. not yet supported by the gui, but still easily doable: http://www.biosolveit.de/tipsntricks/archive/mapref.html finally, maybe not exactly what you need in your specific case, but please note that there are also the "interaction type" constraints. so you could say "i need to see this acceptor interaction with LEU 83" the GUI will guide you a lot in doing all this; in addition it has on-the-fly smarts checking, so you will hopefully not have a hard time coming up with even more complicated expressions. the procedure is 1) load pdb 2) define receptor 3) define pharmacophore btw- the pharm. can also be exported and then used by other tools, e.g., MOE, Sybyl, and an exported PipelinePilot component. i hope this helped. did it? very cordial greetings- marcus Richard Wood rwoodphd:+:msn.com schrieb: > Sent to CCL by: "Richard Wood" [rwoodphd##msn.com] > Hi all, > > I have a series of ligands which I've docked to a protein using > Surflex-Dock as implemented in Sybyl. > > Unfortunately, my results don't explain some experimental observations > so I would like to do some contrained docking. > > I've been looking into FlexX-Pharm, but it seems to only allow one to > constrain an ELEMENT of the ligand to be a certain radius from a > certain atom (which one can choose) in the protein target. For > example, one can pick a nitrogen in a ligand to be within a 3.0 > Angstrom radius of a given protein atom, say. > > This is problematic if your ligand has several nitrogens or carbons in > them, as one cannot pick atom types or atom numbers. I'm wondering if > there is a workaround to this; I'd like to stay with Sybyl as my boss > wants me to use it, and we've decided Glide is not up to our standards. > > To conclude, I would like to be able to pick a particular ligand atom and > constrain it to be a certain distance from a protein atom, that I again > pick, and then dock it. As it stands now, I can only constrain a (any) > nitrogen in my ligand (I think the fact that my ligand is not > introduced at any point, prior to docking, into this process is what is > problematic) to be within a radius of a protein atom, and not a fixed > distance. > > Basically, I want to constrain an imidazole nitrogen > (say) to be 2.4 Angstroms away from an iron atom in a heme group, or a > methyl group to be 3.0 Angstroms from the same atom, and not WITHIN a > radius of this distance, since it can be anywhere from 0 to the > distance I want, and lead to situations I'm seeing now, where the > molecule I'm docking is on top of the heme. > > TIA, > Richard > > > From owner-chemistry@ccl.net Fri Jul 11 20:04:01 2008 From: "Cassandra D Churchill cassandra.churchill%uleth.ca" To: CCL Subject: CCL:G: PCM errors Message-Id: <-37332-080711170339-23849-JgQ3z0Koi+41aPndmjrwpw!=!server.ccl.net> X-Original-From: "Cassandra D Churchill" Date: Fri, 11 Jul 2008 17:03:36 -0400 Sent to CCL by: "Cassandra D Churchill" [cassandra.churchill###uleth.ca] I am running PCM single point calculations in a variety of solvents and these errors come up. I have 2 ring systems separated by more than 7 A. I have tried using the nosymmcav keyword and gave it more memory but this doesnt help. Im using MP2 /6-31G*(0.25). Does anyone have an idea what these errors are and how to fix them? Error #1 Polarizable Continuum Model (PCM) ================================= Model : PCM. Atomic radii : UA0 (Simple United Atom Topological Model). Polarization charges : Total charges. Charge compensation : None. Solution method : Matrix inversion. Cavity : GePol (RMin=0.200 OFac=0.890). Default sphere list used, NSphG= 15. Tesserae with average area of 0.200 Ang**2. Solvent : THF, Eps = 7.580000 Eps(inf)= 1.971000 RSolv = 2.560000 Ang. ------------------------------------------------------------------------------ Consistency failure #1 in Separa. Error termination via Lnk1e in /opt/g03/l301.exe at Tue Jul 1 12:10:45 2008. Job cpu time: 0 days 0 hours 0 minutes 57.3 seconds. File lengths (MBytes): RWF= 13 Int= 0 D2E= 0 Chk= 1 Scr= 1 Error #2 Using symmetry in molecular cavity generation. Separa: There are 2 disjoint cavities, One-electron integrals computed using PRISM. NBasis= 166 RedAO= T NBF= 83 83 NBsUse= 166 1.00D-06 NBFU= 83 83 Harris functional with IExCor= 205 diagonalized for initial guess. ExpMin= 1.61D-01 ExpMax= 4.17D+03 ExpMxC= 6.27D+02 IAcc=1 IRadAn= 1 AccDes= 1.00D-06 HarFok: IExCor= 205 AccDes= 1.00D-06 IRadAn= 1 IDoV=1 ScaDFX= 1.000000 1.000000 1.000000 1.000000 Initial guess orbital symmetries: Occupied (A") (A') (A') (A") (A") (A') (A") (A') (A") (A') (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") Virtual (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A") (A') (A") (A') (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A") (A') (A') (A") (A") (A') (A') (A") (A') (A") (A') (A") (A') (A") (A") (A') (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A') (A") (A") (A') (A') (A") (A') (A") (A') (A") (A') (A") The electronic state of the initial guess is 1-A'. Requested convergence on RMS density matrix=1.00D-08 within 128 cycles. Requested convergence on MAX density matrix=1.00D-06. Requested convergence on energy=1.00D-06. No special actions if energy rises. Inv2 failed in DMIVCL. Error termination via Lnk1e in /opt/g03/l502.exe at Tue Jul 1 12:03:06 2008. Job cpu time: 0 days 0 hours 1 minutes 20.1 seconds. Error #3 ================================= Model : PCM. Atomic radii : UA0 (Simple United Atom Topological Model). Polarization charges : Total charges. Charge compensation : None. Solution method : Matrix inversion. Cavity : GePol (RMin=0.200 OFac=0.890). Default sphere list used, NSphG= 13. Tesserae with average area of 0.200 Ang**2. Solvent : THF, Eps = 7.580000 Eps(inf)= 1.971000 RSolv = 2.560000 Ang. ------------------------------------------------------------------------------ Excessive number of vertices on a tessera. Error termination via Lnk1e in /opt/g03/l301.exe at Thu Jul 3 11:49:45 2008. Job cpu time: 0 days 0 hours 4 minutes 2.0 seconds. Error #4 Polarizable Continuum Model (PCM) ================================= Model : PCM. Atomic radii : UA0 (Simple United Atom Topological Model). Polarization charges : Total charges. Charge compensation : None. Solution method : Matrix inversion. Cavity : GePol (RMin=0.200 OFac=0.890). Default sphere list used, NSphG= 18. Tesserae with average area of 0.200 Ang**2. Solvent : THF, Eps = 7.580000 Eps(inf)= 1.971000 RSolv = 2.560000 Ang. ------------------------------------------------------------------------------ Missed spheres in SBxUpd. Error termination via Lnk1e in /opt/g03/l301.exe at Tue Jul 1 12:13:03 2008. Job cpu time: 0 days 0 hours 0 minutes 9.8 seconds. File lengths (MBytes): RWF= 13 Int= 0 D2E= 0 Chk= 1 Scr= 1 Error #5 Polarizable Continuum Model (PCM) ================================= Model : PCM. Atomic radii : UA0 (Simple United Atom Topological Model). Polarization charges : Total charges. Charge compensation : None. Solution method : Matrix inversion. Cavity : GePol (RMin=0.200 OFac=0.890). Default sphere list used, NSphG= 14. Tesserae with average area of 0.200 Ang**2. Solvent : THF, Eps = 7.580000 Eps(inf)= 1.971000 RSolv = 2.560000 Ang. ------------------------------------------------------------------------------ AdVTs1: ISph= 2865 is engulfed by JSph= 2866 but Ae( 2865) is not yet zero! Error termination via Lnk1e in /opt/g03/l301.exe at Tue Jul 1 12:34:24 2008. Job cpu time: 0 days 0 hours 0 minutes 42.1 seconds. Error #6 Polarizable Continuum Model (PCM) ================================= Model : PCM. Atomic radii : UA0 (Simple United Atom Topological Model). Polarization charges : Total charges. Charge compensation : None. Solution method : Matrix inversion. Cavity : GePol (RMin=0.200 OFac=0.890). Default sphere list used, NSphG= 16. Tesserae with average area of 0.200 Ang**2. Solvent : THF, Eps = 7.580000 Eps(inf)= 1.971000 RSolv = 2.560000 Ang. ----------------------------------------------------------------------------