From mcblimts@leonis.nus.sg Thu Sep 14 02:46:02 1995 Received: from sable.nus.sg for mcblimts@leonis.nus.sg by www.ccl.net (8.6.10/950822.1) id CAA13251; Thu, 14 Sep 1995 02:36:16 -0400 Received: from leonis.nus.sg (leonis.nus.sg [137.132.1.18]) by sable.nus.sg (8.6.10/8.6.9) with ESMTP id OAA06013 for ; Thu, 14 Sep 1995 14:36:09 +0800 Received: (from mcblimts@localhost) by leonis.nus.sg (8.6.10/8.6.9/CNS-3.5) id OAA22606; Thu, 14 Sep 1995 14:36:09 +0800 Date: Thu, 14 Sep 1995 14:36:08 +0800 (SST) From: Lim Teck Sin To: ccl Subject: A summary on Flexible Docking Software Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Hi, I asked about the availablility of flexible docking software recently. Thanks to those who replied on CCEMD, DOCK, BIOSYM and SCULPT packages. (see below) However, I am wondering if there are anymore software (ex: Tripos?) that have/will have such functionality? I will post another summary if I receive more emails on this subject. Thanks!!! best regards - teck sin ----------------------------start of summary----------------------------- Date: Mon, 11 Sep 1995 10:29:45 -0700 (PDT) From: judson richard s To: Lim Teck Sin Subject: Re: CCL:Flexible docking software We have started handing out copies of our general purpose MD code CCEMD which does flexible docking of ligands. Getting the code requires signing a license - at the moment, the only requirement is that it only be used for non-proprietary, non-commercial purposes. I have a users' manual and copies of a couple of papers that I can send if you will give me an address. > | Richard Judson > | Center for Computational Engineering, MS 9214 > | Sandia National Laboratories > | Livermore, CA 94551-0969 > | (510)294-1438 > | (510)294-2234 (FAX) > | email: rsjuds@ca.sandia.gov ----------------------------------------------------------------------- Date: Mon, 11 Sep 1995 10:36:23 -0700 (PDT) From: "Dr. David N. Haney" To: Lim Teck Sin Cc: "Dr. David N. Haney" Subject: Re: CCL:Flexible docking software I have proposed work that will modify Kuntz's DOCK with modal methods to add flexibility. We expect this work to begin soon, but software would not be completed for at least a year or two. ************** David N. Haney, Ph.D. **************** * Haney Associates Phone - 619-566-1127 * * 12010 Medoc Ln. * * San Diego, CA 92131 Fax - 619-586-1481 * ************** Email - haney@netcom.com *************** --------------------------------------------------------------------- Date: Mon, 11 Sep 1995 15:46:26 -0400 (EDT) From: Jie Yuan To: Lim Teck Sin Subject: Re: CCL:Flexible docking software > Just read the newsletter from Biosym. The to-be-released Biosym package will have a molecular mechanics/grid method implemented in Discover that treats the bulk of the receptor as rigid but treats the critical binding site and ligand with molucular mechanics (therefore 'flexible', IMHO). I have not used this product yet. You might want to look at their WWW pages for more info: http://www.biosym.com/ > -- Jie Yuan, PhD - Pharmacology & Cell Biophysics - U. Cincinnati -- > -- Phone: 513-558-2352 -- Fax: x-1169 -- Email: Jie.Yuan@UC.Edu -- > -- P.O. Box 670575, 231 Bethesda Ave., Cincinnati, OH 45267-0575 -- > -- http://www.uc.edu/~yuanj ---------------------------------------------------------------- Date: Tue, 12 Sep 1995 18:40:56 +0200 From: "Klaus J.W.May" To: Lim Teck Sin Subject: Re: CCL:Flexible docking software There is a Software called SCULPT. It might be of help to your work. There are several questions open. What is your understanding of "docking software"? Do you want a automatic procedure which finds also docking sites on a given receptor? Or are you looking for tools which give you answers for possible ligands in a given site? (note from TeckSin: I am looking for tools that can autodock sites too.) Anyhow - SCULPT is a "interactive package". It does REALTIME minimizations of given systems with user definable degrees of restrictions to flexibility and interactive "pull forces" to given atoms or sets of atoms/residues. Not always one wants to have the full system fully flexible. For docking studies, f.i. there is a function called "tug". It keeps the defined set of atoms rigid with respect to themselves. But they start to minimize as soon as some "outer" force is applied to them. One can think of a physical model, which deformes, while squeezed through a hole. but - what do I try to explain... You can have a demoversion free of cost. Downloadable via internet. It runs on SGI. A brandnew Powermac version is available soon. look at the homepage http://www.intsim.com/~isigen and learn more about SCULPT Good luck! Klaus J.W. May e-mail: kmay@trans.net May & Partner Phone/Fax: xx49-(89) 333 569 SciTech Consult Mobile national: 0171-80 80 900 Mandlstr. 15 international: xx49-1712-80 80 900 D - 80802 Munich GERMANY --------------------------------------------------------------------- cxl@iris158.biosym.com> Newsgroups: biosym.chemistry Subject: CCL:Flexible docking software In the 950 release from Biosym/MSI scheduled for next month, there is a new product named Affinity which does flexible docking. Both the ligand and receptor are flexible. It is an energy-based method and it combines the merits of Monte Carlo, minimization and dyanmics. It also uses the molecular mechanics/grid method of Luty et al. (JCC, 16, 454, 1995) to speed up the calculation and to include implicit solvation model of Stouten et al. (Mol. Simulations, 10, 97, 1993). For more infomation, please contact your local Biosym/MSI sales office. Congxin Liang Biosym/MSI -------------------------------------------------------------------- Date: Wed, 13 Sep 1995 12:21:57 -0800 From: "Mark C. Surles" To: Lim Teck Sin Cc: chemistry@ccl.net Subject: Re: CCL:Flexible docking software Sculpt from Interactive Simulations provides both flexible receptor and ligand during real-time, user-guided docking. Flexibility is a function of energy minimization. See the Flavin/Flavodoxin, HIV protease, and Beta lactamase examples in the demos. Demos are available via the WWW at http://www.intsim.com/~isigen or end email to intsim-support@intsim.com. Mark Surles Interactive Simulations, Inc. Phone: (619) 658-9462 5330 Carroll Canyon Road FAX: (619) 658-9463 Suite 203 Email: surles@intsim.com San Diego, CA 92121 URL: http://www.intsim.com/~isigen ------------------------------------------------------------------------ Date: Wed, 13 Sep 1995 18:12:49 -0400 From: Nick Hodge To: chemistry@ccl.net Subject: CCL:Flexible docking software A brief expansion on Congxin's note regarding flexible docking As indicated, the method was developed at DuPont Merck and employs molecular dynamics to 'fly' a ligand into the active site of an enzyme. The active site is flexible and represented explicitly, an intermediate region of the enzyme is restrained, and a grid represents the rest of the enzyme. An atom-based solvation term is added (Stouten et al. Mol. Simulations, 10, 97, 1993). The initial implementation (Luty et al., JCC, 16, 454, 1995) was able to reproduce the crystallographic orientation of benzamidine in trypsin rapidly and accurately, starting from random orientations outside of the active site; similarly, leucine hydroxamic acid finds its way into the crystallographically observed orientation in thermolysin (Wasserman and Hodge, Proteins: Structure, Function and Genetics, in press). In neither case do we attempt to correlate energies with the experimentally observed conformations, but preliminary analysis suggests that some correlation is possible. The successful extension to thermolysin and a more flexible inhibitor is also encouraging. However, the method has to be considered preliminary and in need of extensive testing and improvement. The Biosym implementation includes a Monte Carlo conformation/location generator and minimization to find optimum docked sites, as well the Discover 3.0 environment and cvff or cff91 forcefields; Amber is still being used as well at DuPont Merck. The results with cvff are similar, although not identical, to Amber in the limited comparisons that have been run. We are very interested in comments, suggestions, enhancements etc. to the method. We should also make clear that it is an extension of earlier and continuing docking protocols of Goodford, Olson, Kuntz, Bohm etc. and relies on many of their observations and ideas. --------------------------end of summary------------------------------- From mcblimts@leonis.nus.sg Thu Sep 14 02:36:25 1995 Received: from sable.nus.sg for mcblimts@leonis.nus.sg by www.ccl.net (8.6.10/950822.1) id CAA13251; Thu, 14 Sep 1995 02:36:16 -0400 Received: from leonis.nus.sg (leonis.nus.sg [137.132.1.18]) by sable.nus.sg (8.6.10/8.6.9) with ESMTP id OAA06013 for ; Thu, 14 Sep 1995 14:36:09 +0800 Received: (from mcblimts@localhost) by leonis.nus.sg (8.6.10/8.6.9/CNS-3.5) id OAA22606; Thu, 14 Sep 1995 14:36:09 +0800 Date: Thu, 14 Sep 1995 14:36:08 +0800 (SST) From: Lim Teck Sin To: ccl Subject: A summary on Flexible Docking Software Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Status: RO Hi, I asked about the availablility of flexible docking software recently. Thanks to those who replied on CCEMD, DOCK, BIOSYM and SCULPT packages. (see below) However, I am wondering if there are anymore software (ex: Tripos?) that have/will have such functionality? I will post another summary if I receive more emails on this subject. Thanks!!! best regards - teck sin ----------------------------start of summary----------------------------- Date: Mon, 11 Sep 1995 10:29:45 -0700 (PDT) From: judson richard s To: Lim Teck Sin Subject: Re: CCL:Flexible docking software We have started handing out copies of our general purpose MD code CCEMD which does flexible docking of ligands. Getting the code requires signing a license - at the moment, the only requirement is that it only be used for non-proprietary, non-commercial purposes. I have a users' manual and copies of a couple of papers that I can send if you will give me an address. > | Richard Judson > | Center for Computational Engineering, MS 9214 > | Sandia National Laboratories > | Livermore, CA 94551-0969 > | (510)294-1438 > | (510)294-2234 (FAX) > | email: rsjuds@ca.sandia.gov ----------------------------------------------------------------------- Date: Mon, 11 Sep 1995 10:36:23 -0700 (PDT) From: "Dr. David N. Haney" To: Lim Teck Sin Cc: "Dr. David N. Haney" Subject: Re: CCL:Flexible docking software I have proposed work that will modify Kuntz's DOCK with modal methods to add flexibility. We expect this work to begin soon, but software would not be completed for at least a year or two. ************** David N. Haney, Ph.D. **************** * Haney Associates Phone - 619-566-1127 * * 12010 Medoc Ln. * * San Diego, CA 92131 Fax - 619-586-1481 * ************** Email - haney@netcom.com *************** --------------------------------------------------------------------- Date: Mon, 11 Sep 1995 15:46:26 -0400 (EDT) From: Jie Yuan To: Lim Teck Sin Subject: Re: CCL:Flexible docking software > Just read the newsletter from Biosym. The to-be-released Biosym package will have a molecular mechanics/grid method implemented in Discover that treats the bulk of the receptor as rigid but treats the critical binding site and ligand with molucular mechanics (therefore 'flexible', IMHO). I have not used this product yet. You might want to look at their WWW pages for more info: http://www.biosym.com/ > -- Jie Yuan, PhD - Pharmacology & Cell Biophysics - U. Cincinnati -- > -- Phone: 513-558-2352 -- Fax: x-1169 -- Email: Jie.Yuan@UC.Edu -- > -- P.O. Box 670575, 231 Bethesda Ave., Cincinnati, OH 45267-0575 -- > -- http://www.uc.edu/~yuanj ---------------------------------------------------------------- Date: Tue, 12 Sep 1995 18:40:56 +0200 From: "Klaus J.W.May" To: Lim Teck Sin Subject: Re: CCL:Flexible docking software There is a Software called SCULPT. It might be of help to your work. There are several questions open. What is your understanding of "docking software"? Do you want a automatic procedure which finds also docking sites on a given receptor? Or are you looking for tools which give you answers for possible ligands in a given site? (note from TeckSin: I am looking for tools that can autodock sites too.) Anyhow - SCULPT is a "interactive package". It does REALTIME minimizations of given systems with user definable degrees of restrictions to flexibility and interactive "pull forces" to given atoms or sets of atoms/residues. Not always one wants to have the full system fully flexible. For docking studies, f.i. there is a function called "tug". It keeps the defined set of atoms rigid with respect to themselves. But they start to minimize as soon as some "outer" force is applied to them. One can think of a physical model, which deformes, while squeezed through a hole. but - what do I try to explain... You can have a demoversion free of cost. Downloadable via internet. It runs on SGI. A brandnew Powermac version is available soon. look at the homepage http://www.intsim.com/~isigen and learn more about SCULPT Good luck! Klaus J.W. May e-mail: kmay@trans.net May & Partner Phone/Fax: xx49-(89) 333 569 SciTech Consult Mobile national: 0171-80 80 900 Mandlstr. 15 international: xx49-1712-80 80 900 D - 80802 Munich GERMANY --------------------------------------------------------------------- cxl@iris158.biosym.com> Newsgroups: biosym.chemistry Subject: CCL:Flexible docking software In the 950 release from Biosym/MSI scheduled for next month, there is a new product named Affinity which does flexible docking. Both the ligand and receptor are flexible. It is an energy-based method and it combines the merits of Monte Carlo, minimization and dyanmics. It also uses the molecular mechanics/grid method of Luty et al. (JCC, 16, 454, 1995) to speed up the calculation and to include implicit solvation model of Stouten et al. (Mol. Simulations, 10, 97, 1993). For more infomation, please contact your local Biosym/MSI sales office. Congxin Liang Biosym/MSI -------------------------------------------------------------------- Date: Wed, 13 Sep 1995 12:21:57 -0800 From: "Mark C. Surles" To: Lim Teck Sin Cc: chemistry@ccl.net Subject: Re: CCL:Flexible docking software Sculpt from Interactive Simulations provides both flexible receptor and ligand during real-time, user-guided docking. Flexibility is a function of energy minimization. See the Flavin/Flavodoxin, HIV protease, and Beta lactamase examples in the demos. Demos are available via the WWW at http://www.intsim.com/~isigen or end email to intsim-support@intsim.com. Mark Surles Interactive Simulations, Inc. Phone: (619) 658-9462 5330 Carroll Canyon Road FAX: (619) 658-9463 Suite 203 Email: surles@intsim.com San Diego, CA 92121 URL: http://www.intsim.com/~isigen ------------------------------------------------------------------------ Date: Wed, 13 Sep 1995 18:12:49 -0400 From: Nick Hodge To: chemistry@ccl.net Subject: CCL:Flexible docking software A brief expansion on Congxin's note regarding flexible docking As indicated, the method was developed at DuPont Merck and employs molecular dynamics to 'fly' a ligand into the active site of an enzyme. The active site is flexible and represented explicitly, an intermediate region of the enzyme is restrained, and a grid represents the rest of the enzyme. An atom-based solvation term is added (Stouten et al. Mol. Simulations, 10, 97, 1993). The initial implementation (Luty et al., JCC, 16, 454, 1995) was able to reproduce the crystallographic orientation of benzamidine in trypsin rapidly and accurately, starting from random orientations outside of the active site; similarly, leucine hydroxamic acid finds its way into the crystallographically observed orientation in thermolysin (Wasserman and Hodge, Proteins: Structure, Function and Genetics, in press). In neither case do we attempt to correlate energies with the experimentally observed conformations, but preliminary analysis suggests that some correlation is possible. The successful extension to thermolysin and a more flexible inhibitor is also encouraging. However, the method has to be considered preliminary and in need of extensive testing and improvement. The Biosym implementation includes a Monte Carlo conformation/location generator and minimization to find optimum docked sites, as well the Discover 3.0 environment and cvff or cff91 forcefields; Amber is still being used as well at DuPont Merck. The results with cvff are similar, although not identical, to Amber in the limited comparisons that have been run. We are very interested in comments, suggestions, enhancements etc. to the method. We should also make clear that it is an extension of earlier and continuing docking protocols of Goodford, Olson, Kuntz, Bohm etc. and relies on many of their observations and ideas. --------------------------end of summary------------------------------- From jkl@ccl.net Thu Sep 14 10:31:08 1995 Received: from bedrock.ccl.net for jkl@ccl.net by www.ccl.net (8.6.10/950822.1) id KAA18824; Thu, 14 Sep 1995 10:16:36 -0400 Received: from csb0.IPC.PKU.EDU.CN for zhy@csb0.IPC.PKU.EDU.CN by bedrock.ccl.net (8.6.10/950822.1) id KAA18031; Thu, 14 Sep 1995 10:16:31 -0400 Received: by csb0.IPC.PKU.EDU.CN (920330.SGI/940406.SGI.AUTO) for chemistry@ccl.net id AA26149; Thu, 14 Sep 95 21:59:50 -0700 Date: Thu, 14 Sep 1995 21:59:48 -0700 (PDT) From: Zhang Hongyu To: COMP_CHEM_LIST Subject: Cluster according to internal coordinates Message-Id: Mime-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear CCL'ers, I've got from a simulated annealing process a group of conformations of a penta-ptide with 3D coordinates, and want to cluster them according to internal coordinates, i.e. value of Phi and Psi angle, but I haven't found the relative function in SYBYL or QUANTA. Can anyone tell me where to find suitable softwares ? BTW, I also want to get the standard of dividing Ramanchandra graph (explicit value), i.e., if I got a pair of Phi-Psi value, how can I tell whether it fall into A,D,or D*? Many thanks in advance ! Henry ---------------------------------------------------------------------- Henry Hongyu Zhang, Ph.D. student | email: zhy@ipc.pku.edu.cn Molecule Design Laboratory | zhy@pschnetware.pku.edu.cn Institute of Physical Chemistry | Tel: 8610-2501490 Peking University | Fax: 8610-2501725 Peking 100871 , China | ----------- Too hard, to be broken Too soft, to be worthless ------------ Old Chinese Saying From jkl@ccl.net Thu Sep 14 13:16:10 1995 Received: from bedrock.ccl.net for jkl@ccl.net by www.ccl.net (8.6.10/950822.1) id NAA22609; Thu, 14 Sep 1995 13:10:54 -0400 Received: from mailhub.cc.columbia.edu for shenkin@still3.chem.columbia.edu by bedrock.ccl.net (8.6.10/950822.1) id NAA19792; Thu, 14 Sep 1995 13:10:52 -0400 Received: from still3.chem.columbia.edu by mailhub.cc.columbia.edu with SMTP id AA03498 (5.65c+CU/IDA-1.4.4/HLK for <@mailhub.cc.columbia.edu:chemistry@ccl.net>); Thu, 14 Sep 1995 13:07:23 -0400 Received: by still3.chem.columbia.edu (931110.SGI/930416.SGI.AUTO) for @mailhub.cc.columbia.edu:zhy@csb0.IPC.PKU.EDU.CN id AA19363; Thu, 14 Sep 95 12:37:15 -0400 Date: Thu, 14 Sep 95 12:37:15 -0400 From: shenkin@still3.chem.columbia.edu (Peter Shenkin) Message-Id: <9509141637.AA19363@still3.chem.columbia.edu> To: COMP_CHEM_LIST , Zhang Hongyu Subject: Re: CCL:Cluster according to internal coordinates > From: Zhang Hongyu > Subject: CCL:Cluster according to internal coordinates > I've got from a simulated annealing process a group of conformations of a > penta-ptide with 3D coordinates, and want to cluster them according to > internal coordinates, i.e. value of Phi and Psi angle, but I haven't found > the relative function in SYBYL or QUANTA. Can anyone tell me where to find > suitable softwares ? Our program, XCluster, is designed to do exactly this. It's included with MacroModel, which isn't free, but is very cheap to academics. For further info, "finger mmod@still3.chem.columbia.edu". If you visit our WWW home page and work your way down to a description of the XCluster program, you'll see some images that show what clusters of conformations look like if the ensemble indeed exhbits strong clustering. Our home page is: http://www.cc.columbia.edu/~chempub/mmod/mmod.html XCluster can work in either torsional space or in Cartesian space; the user decides at run-time. You can read more about XCluster in: Shenkin & McDonald, J. Comput. Chem., v.15, pp.899-916, 1994. Also, the latest version of MacroModel, Version 5.0, includes converters that translate from SYBYL Mol2 format to MacroModel format (and vice versa) -- so if you've been using SYBYL, it ought to be easy to get your conformations into a format that MacroModel can understand. > BTW, I also want to get the standard of dividing Ramanchandra graph > (explicit value), i.e., if I got a pair of Phi-Psi value, how can I tell > whether it fall into A,D,or D*? XCluster doesn't do this for you; sorry. But the way I'd do this is to print out the Phi-Psi values (MacroModel can do this for you). Then calculate the distance of each pair to the "generic" pair value for the A, D and D* regions, taking the periodicity of angle space into account. The "generic" pair value a given Phi-Psi pair is closest to defines which region it belongs to. -P. ******** When somebody says, "It's a matter of principle,"... ******** *Peter S. Shenkin, Box 768 Havemeyer Hall, Chemistry, Columbia Univ.,* *NY, NY 10027; shenkin@columbia.edu; (212)854-5143; FAX: 678-9039* ************ ...it's a sure sign he wants the whole pie. *************