From chemistry-request@server.ccl.net Mon Jan 13 08:51:40 2003 Received: from fzkmail2.fzk.de ([141.52.27.52]) by server.ccl.net (8.11.6/8.11.0) with SMTP id h0DDpd429727 for ; Mon, 13 Jan 2003 08:51:40 -0500 Received: FROM FZKMSX4.ka.fzk.de BY fzkmail2.fzk.de ; Mon Jan 13 14:51:38 2003 +0100 Received: from int.fzk.de ([141.52.95.92]) by FZKMSX4.ka.fzk.de with Microsoft SMTPSVC(5.0.2195.4453); Mon, 13 Jan 2003 14:51:38 +0100 Sender: rubner@ccl.net Message-ID: <3E22C464.89371C88@int.fzk.de> Date: Mon, 13 Jan 2003 14:51:32 +0100 From: Oliver Rubner X-Mailer: Mozilla 4.76 [de] (X11; U; Linux 2.4.0-4GB i686) X-Accept-Language: de-DE, en MIME-Version: 1.0 To: chemistry@ccl.net Subject: New TURBOMOLE release V5-6 Content-Type: text/plain; charset=UTF-7 Content-Transfer-Encoding: 7bit X-OriginalArrivalTime: 13 Jan 2003 13:51:38.0225 (UTC) FILETIME=[E4C92610:01C2BB0A] Karlsruhe, December 2002 Dear colleagues, we would like to inform you that TURBOMOLE version V5-6 is now available. New features include: * Excited state properties, geometry optimization, and (numerical) force constant calculations using TDDFT, CIS, and RPA [F. Furche, R. Ahlrichs, J. Chem. Phys. 117 (2002), 7433] * RI-CC2 one-electron properties for excited states [C. H+AOQ-ttig, A. K+APY-hn, J. Chem. Phys. 117 (2002), 6939] * RI-CC2 gradients for ground states [C. H+AOQ-ttig, submitted] * Improved analytic second derivative calculations (including partial use of the RI approximation) [P. Deglmann, F. Furche, R. Ahlrichs, Chem. Phys. Lett. 362 (2002), 511] * Direct iterative methods for computing the lowest vibrational modes of a molecule [P. Deglmann, F. Furche, J. Chem. Phys. 117 (2002), 9535] * Efficient calculation of optical rotations using TDDFT [S. Grimme, F. Furche, R. Ahlrichs, Chem. Phys. Lett. 361 (2002), 321] * "O(N)-RIDFT" using the multipole accelerated RI-J approximation [M. Sierka, A. Hogekamp, R. Ahlrichs, submitted] * Occupation number optimization using (pseudo-Fermi) thermal smearing * RI-JK approximation for Hartree-Fock including highly accurate optimized auxiliary basis sets [F. Weigend, Phys. Chem. Chem. Phys. 4 (2002), 4285] * Transition state optimization (trust radius minimization) * Exact exchange Kohn-Sham methods using the LHF approximation [F. Della Sala, A. G+APY-rling, J. Chem. Phys. 115 (2001), 5718; J. Chem. Phys. 116 (2002), 5374] * Better interfaces to graphics programs * Various other improvements Please refer to http://www.turbomole.de for further details and terms of use, or send an e-mail to info@turbomole.com. Yours sincerely, Quantum Chemistry Group, Karlsruhe From chemistry-request@server.ccl.net Mon Jan 13 11:06:23 2003 Received: from schrodinger.com ([192.156.98.99]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DG6M400822 for ; Mon, 13 Jan 2003 11:06:23 -0500 Received: from tandoori (root@tandoori.schrodinger.com [216.216.237.99]) by schrodinger.com (8.8.5/8.8.5) with ESMTP id IAA18512 for ; Mon, 13 Jan 2003 08:06:21 -0800 Received: from janice.schrodinger.com (janice.schrodinger.com [216.216.237.68]) by tandoori (8.8.5/8.8.5) with ESMTP id LAA28964 for ; Mon, 13 Jan 2003 11:06:17 -0500 Received: from localhost (dixon@localhost) by janice.schrodinger.com (8.11.6/8.11.6) with ESMTP id h0DG6LF30313 for ; Mon, 13 Jan 2003 11:06:21 -0500 Date: Mon, 13 Jan 2003 11:06:21 -0500 (EST) From: Steve Dixon To: chemistry@ccl.net Subject: Ligand-based Design Survey - Win a Palm m515! Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Schrodinger, Inc. is conducting a survey of scientists who use ligand-based design software. The goal of the survey is to help us understand what is most important to customers as we work toward integrating our scientific expertise into a ligand-based design application. The survey should take less than 15 minutes to complete, and respondents will be entered into a drawing where first prize is a Palm m515, and second prize is a $50 amazon.com gift certificate. To ensure that we can develop the best product possible to meet your needs, please take a few minutes to complete the survey at: http://www.schrodinger.com/Surveys/LBDDSurvey.htm Thank you, and good luck in the drawing. Steven L. Dixon, Ph.D. Product Manager, Ligand-Based Drug Design Schrodinger, Inc. dixon@schrodinger.com From chemistry-request@server.ccl.net Sun Jan 12 14:31:59 2003 Received: from mail.staff.site.ntu.edu.au ([138.80.69.54]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0CJVw421919 for ; Sun, 12 Jan 2003 14:31:58 -0500 Received: from mail.staff.site.ntu.edu.au ([138.80.49.23]) by mail.staff.site.ntu.edu.au with Microsoft SMTPSVC(5.0.2195.5329); Sun, 12 Jan 2003 19:05:02 +0930 Received: by mail.staff.site.ntu.edu.au (sSMTP sendmail emulation); Sun, 12 Jan 2003 19:04:03 +0930 Date: Sun, 12 Jan 2003 19:04:03 +0930 From: Brian Salter-Duke To: Comp Chem List Subject: Launching rasmol from linux mozilla Message-ID: <20030112093403.GA15474@monster.ntu.edu.au> Mail-Followup-To: Comp Chem List Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Disposition: inline User-Agent: Mutt/1.4i X-OriginalArrivalTime: 12 Jan 2003 09:35:03.0351 (UTC) FILETIME=[E2500C70:01C2BA1D] I am on a linux machine (RH 7.2, but I do not think that is important). I am trying to get Rasmol to be automatically launched to display pdb files from my browser. I am using netscape:- Netscape 4.78/U.S., 25-Jun-01; (c) 1995-2000 Netscape Communications Corp. and mozilla:- Mozilla/5.0 (X11; U; Linux i686; en-US; rv:0.9.2.1) Gecko/20010901, build 2001090111 I prefer mozilla. I have gone through the process of setting rasmol as the helper application. For mozilla I took the advice from:- http://www.dkfz-heidelberg.de/spec/sweet2/doc/plugin/fhelper.html and called rasmol from a wrapper script. Rasmol is:- Version 2.7.2.1 April 2001. Now I want rasmol to open in three circumstances:- 1. Reading a pdb file of a web page over the internet, when it has the MIME type 'chemical/x-pdb'. 2. Reading a local pdb file. 3. Reading a local pdb file but with the browser opened with the file name on the command line from a script. The local file is actually in /tmp from a mail attachment. I want rasmol to open from the browser the mail attachment if it is a pdb file. I can open rasmol direct, but I want to later explore other possible pluggins as chime is not available in linux. The problem is that with mozilla only (1) works. With netscape all three work. With mozilla (2) and (3) just display the text of the pdb file in the browser window and rasmol is not opened. It looks as if solving (2) will get (3) working. Note that if I save a pdb file off the internet and then try to open it from the 'open file' in the mozilla 'file' menu, it does not open rasmol even though it does directly. In (3) I use 'netscape -remote "openFile($1)"' if netscape is already open or 'netscape $1' if it is not running. $1 is the URL. For mozilla I used the same, but had to add 'file://' to the front of $1 to even get the text displayed. Does any one have any pointers to what is wrong? What do I have to do different for mozilla? Regards, Brian. -- Brian Salter-Duke (Brian Duke) b_duke@octa4.net.au Honorary Fellow in Chemistry, NT University, Darwin, NT 0909, Australia. Post: Box 1028, Humpty Doo, NT 0836, Australia. Phone 08-89881600. Fax 08-89881302. http://www.octa4.net.au/linden/brian/ From chemistry-request@server.ccl.net Mon Jan 13 11:44:11 2003 Received: from f04n01.cac.psu.edu ([128.118.141.31]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DGiA402066 for ; Mon, 13 Jan 2003 11:44:11 -0500 Received: from psu.edu (cornea.chem.psu.edu [128.118.172.87]) by f04n01.cac.psu.edu (8.9.3/8.9.3) with ESMTP id LAA55186 for ; Mon, 13 Jan 2003 11:44:10 -0500 Message-ID: <3E22ECE9.12D85D1@psu.edu> Date: Mon, 13 Jan 2003 11:44:25 -0500 From: Ed Brothers Reply-To: enb108@psu.edu Organization: PSU Merz Group X-Mailer: Mozilla 4.61 (Macintosh; I; PPC) X-Accept-Language: en,pdf MIME-Version: 1.0 To: chemistry@ccl.net Subject: Question about the CPHF Content-Type: text/plain; charset=us-ascii; x-mac-type="54455854"; x-mac-creator="4D4F5353" Content-Transfer-Encoding: 7bit I sent something similar to this question before Christmas, but I thought I would try the CCL again as I am still a bit stuck. I am trying to implement the CPHF in order to calculate the second derivative of the energy with respect to nuclear motion. In addition to the famous Pople article from 1979, I have been using Frisch, Head-Gordon, and Pople, Chem. Phys. 141, 1990, p 189-196. My difficulty lies in forming the first derivative of the density matrix. I am currently conducting test calculations on an H2 molecule at the equilibrium geometry. Each atom has one s type basis function on it. It would appear to me that the first derivative of P(1,1) and P(2,2) (where P is the denisty matrix) should be equal, and finite difference calculations seem to bear this out. But I get a unphysical answer using the CPHF, which means I must be using it incorrectly. Here's where my problem arises: As there is only one occupied orbital, the elements of the density matrix are simply: (1) P(mu,nu) = c(mu,1) c(nu,1) Where c is the MO orbital coefficients, and mu and nu refer to atomic basis functions. Taking the derivative: (2) dP(mu,nu)/dx = dc(mu,1)/dx c(nu,1) + dc(nu,1)/dx c(mu,1) Now according to the Pople paper from 1979: (3) dc(nu,1)/dx = (Sum over q=1, N) c(nu,q) u(q,1) Where u are the values derived from the CPHF. (This eq. 29 in the paper). Since q can equal either 1 or 2: (4) dc(nu,1)/dx = c(nu,1) u(1,1) + c(nu,2) u(2,1) Substituting (4) into (2): (5) dP(mu,nu)/dx = [c(mu,1) u(1,1) + c(mu,2) u(2,1)]c(nu,1) + [c(nu,1) u(1,1) + c(nu,2) u(2,1)] c(mu,1) Now lets look at two specific derivative density matrix elements, dP(1,1)/dx and dP(2,2)/dx, which should be equal. (6a) dP(1,1)/dx = [c(1,1) u(1,1) + c(1,2) u(2,1)]c(1,1) + [c(1,1)u(1,1) + c(1,2) u(2,1)] c(1,1) (6b) dP(2,2)/dx = [c(2,1) u(1,1) + c(2,2) u(2,1)]c(2,1) + [c(2,1)u(1,1) + c(2,2) u(2,1)] c(2,1) Rearranging: (7a) dP(1,1)/dx = 2 c(1,1)^2 u(1,1) + 2 c(1,1) c(1,2) u(2,1) (7b) dP(2,2)/dx = 2 c(2,1)^2 u(1,1) + 2 c(2,2) c(2,1) u(2,1) > From the the coefficients of the first MO, we know c(1,1) = c(2,1). From the second MO, we know that c(1,2) = -c(2,2). If we substitute this into (7) we get: (8a) dP(1,1)/dx = 2 c(1,1)^2 u(1,1) + 2 c(1,1) c(1,2) u(2,1) (8b) dP(2,2)/dx = 2 c(1,1)^2 u(1,1) - 2 c(1,2) c(1,2) u(2,1) Thus it would appear that dP(1,1)/dx .ne. dP(2,2)/dx. This is incorrect. I am guessing my error is in the way I use (3), but I am unsure as to what I am doing wrong. Any help you can give me would be enormously appreciated. Thanks for your time! Ed Brothers. Merz Group. PSU. From chemistry-request@server.ccl.net Mon Jan 13 11:46:13 2003 Received: from cuces.unisi.it ([193.205.4.2]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DGkC402141 for ; Mon, 13 Jan 2003 11:46:12 -0500 Received: from CONVERSION-DAEMON.unisi.it by unisi.it (PMDF V6.1-1 #30546) id <01KR710DUZS00032SO@unisi.it> for chemistry@ccl.net; Mon, 13 Jan 2003 17:46:03 +0100 (MET) Received: from student.unisi.it (octane1.ctf.unisi.it [172.16.3.84]) by unisi.it (PMDF V6.1-1 #30546) with ESMTPA id <01KR710BFORG003MPN@unisi.it> for chemistry@ccl.net; Mon, 13 Jan 2003 17:45:59 +0100 (MET) Date: Mon, 13 Jan 2003 17:42:05 +0100 From: Lucilla Angeli Subject: Water molecules Sender: lucilla@unisi.it To: chemistry@ccl.net Message-id: <3E22EC5C.B47DC6B2@student.unisi.it> MIME-version: 1.0 X-Mailer: Mozilla 4.7C-SGI [en] (X11; I; IRIX64 6.5 IP30) Content-type: multipart/alternative; boundary="Boundary_(ID_YdSAX3lTFD1j1BEiv/oq8w)" X-Accept-Language: en --Boundary_(ID_YdSAX3lTFD1j1BEiv/oq8w) Content-type: text/plain; charset=us-ascii Content-transfer-encoding: 7BIT Dear CCLers I have to do a docking study of some inhibitors of an enzyme, but I don't know what to do with the water molecules. Could you suggest to me a general method to handle these water molecules found in the crystal structure (PDB) of enzymes? Have I to consider them in my simulations? Or, have I to ignore them? Could you advise any papers about this argument? I'll be grateful for any suggestion. Lucilla -- ********************************* Lucilla Angeli c/o Prof. Botta Dip. Farmaco Chimico Tecnologico Universita' degli Studi Di Siena Via Aldo Moro I-53100 Siena, Italy Phone: ++39 0577 234307 Fax: ++39 0577 234333 ********************************** --Boundary_(ID_YdSAX3lTFD1j1BEiv/oq8w) Content-type: text/html; charset=us-ascii Content-transfer-encoding: 7BIT Dear CCLers
I have to do a docking study of some inhibitors of an enzyme, but I don't know what to do with the water molecules.
Could you suggest to me a general method to handle these water molecules found in the crystal structure (PDB) of enzymes?
Have I to consider them in my simulations?
Or, have I to ignore them?
Could you advise any papers about this argument?
I'll be grateful for any suggestion.
Lucilla 
-- 

*********************************
Lucilla Angeli  
c/o Prof. Botta
Dip. Farmaco Chimico Tecnologico
Universita' degli Studi Di Siena
Via Aldo Moro
I-53100 Siena, Italy
Phone:  ++39 0577 234307
Fax:    ++39 0577 234333
**********************************
  --Boundary_(ID_YdSAX3lTFD1j1BEiv/oq8w)-- From chemistry-request@server.ccl.net Mon Jan 13 12:36:11 2003 Received: from hermes.csd.unb.ca ([131.202.3.20]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DHaB403489 for ; Mon, 13 Jan 2003 12:36:11 -0500 Received: from mailserv2 (mailserv.unb.ca [131.202.3.23]) by hermes.csd.unb.ca (8.12.3/8.12.3) with SMTP id h0DHaAYl006027 for ; Mon, 13 Jan 2003 13:36:10 -0400 (AST) Received: FROM pop.unb.ca BY mailserv2 ; Mon Jan 13 13:36:09 2003 -0400 Received: from webmail1 (webmail1.unb.ca [131.202.130.26]) by pop.unb.ca (8.11.6+Sun/8.11.6) with ESMTP id h0DHa9C11176; Mon, 13 Jan 2003 13:36:09 -0400 (AST) X-WebMail-UserID: l72k6 Date: Mon, 13 Jan 2003 13:36:08 -0400 Sender: Robert Flight From: Robert Flight To: Computational Chemistry List , Lucilla Angeli X-EXP32-SerialNo: 00003025, 00003442 Subject: RE: CCL:Water molecules Message-ID: <3E2846F2@webmail1> Mime-Version: 1.0 Content-Type: text/plain; charset="US-ASCII" Content-Transfer-Encoding: 7bit X-Mailer: WebMail (Hydra) SMTP v3.61.08 Dear Lucilla, Most docking programs available are used with the assumption that the docking is done with the water molecules absent. Many docking programs includes an implicit solvation function that tries to account for solvation affects of the ligand and the receptor, but cannot account for any molecule specific interactions such as water molecules that act as "bridges" between the ligand and the receptor (an exception to this is a paper on FLEXX, Rarey, M. et al. (1999) PROTEINS, vol 34, p 17-28). Depending on the enzyme system, individual water molecules may be very important. If you have PDB files of the enzyme with various inhibitors with the enzyme, I would try docking with and without the water molecules included. If you dont have any files like this, there are some options reported in the literature. GRID - can be used to look at potential water sites in the receptor (Goodford, P.J. (1985) J. Med. Chem., vol 28, 849-857 and Minke, W.E. et al. (1999) J. Med. Chem., vol 42, p 1778-1788) Consolv - tries to predict which waters in the receptor will be displaced upon ligand binding (Raymer, M.L. et al. (1997) J. Mol. Biol. vol 265, p 445-464, also see http://www.bch.msu.edu/labs/kuhn/web/docs/consolv_doc.html) You can find a lot more by searching for water and docking in any decent literature database. I havent found anything about a "general" method to handle water molecules in the ligand that will work for all purposes. Good luck with your study. Cheers, Robert >===== Original Message From Lucilla Angeli ===== >Dear CCLers >I have to do a docking study of some inhibitors of an enzyme, but I >don't know what to do with the water molecules. >Could you suggest to me a general method to handle these water molecules >found in the crystal structure (PDB) of enzymes? >Have I to consider them in my simulations? >Or, have I to ignore them? >Could you advise any papers about this argument? >I'll be grateful for any suggestion. >Lucilla > >-- > >********************************* >Lucilla Angeli >c/o Prof. Botta >Dip. Farmaco Chimico Tecnologico >Universita' degli Studi Di Siena >Via Aldo Moro >I-53100 Siena, Italy >Phone: ++39 0577 234307 >Fax: ++39 0577 234333 >********************************** ******************************** Robert Flight Masters Student Department of Chemistry University of New Brunswick Fredericton, NB Canada E3B 6E2 e-mail: robert.flight@unb.ca ******************************** "A computer terminal is not some clunky old television with a typewriter in front of it. It is an interface where the mind and body can connect with the universe and move bits of it about." -- Hitch Hikers Guide to the Galaxy From chemistry-request@server.ccl.net Mon Jan 13 12:32:51 2003 Received: from GWIA.HSC.WVU.EDU ([157.182.105.18]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DHWp403420 for ; Mon, 13 Jan 2003 12:32:51 -0500 Received: from HSC-DOM5-MTA by GWIA.HSC.WVU.EDU with Novell_GroupWise; Mon, 13 Jan 2003 12:32:46 -0500 Message-Id: X-Mailer: Novell GroupWise Internet Agent 6.0.2 Date: Mon, 13 Jan 2003 12:32:19 -0500 From: "Peter Gannett" To: , Cc: , Subject: Re: electrostatic potential calculations Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Disposition: inline Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id h0DHWp403421 All: The correct address for MEAD is: http://www.scripps.edu/bashford/ Pete Gannett >>> Andreas Svrcek-Seiler 01/11/03 11:43AM >>> Hi, > Does anyone know a freeware for calculating the electrostatic potential > distribution on macromolecule (something like DelPHI). As far as I know ...yes, MEAD is free (get it from ftp://ftp.scripps.edu/pub/electrostatics/ ) ->cool program suite, very flexible, easy to use and fortran-free (!), but sparsely documented. an alternative might be apbs ( go to http://agave.wustl.edu/apbs/), which is still beta but looks promising (I've compiled but not really tried it). I hope that helps, good luck Andreas -- ))))) ((((( ( O O ) -------oOOO--(_)--OOOo----------------------------------------------------- o Wolfgang Andreas Svrcek-Seiler o (godzilla) svrci@tbi.univie.ac.at .oooO Tel.:01-4277-52733 ( ) Oooo. -------\ (----( )-------------------------------------------------------- \_) ) / (_/ From chemistry-request@server.ccl.net Mon Jan 13 13:42:48 2003 Received: from fulcrum.physbio.mssm.edu ([146.203.4.14]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DIgl406632 for ; Mon, 13 Jan 2003 13:42:47 -0500 Received: from mezei (helo=localhost) by fulcrum.physbio.mssm.edu with local-esmtp (Exim 3.11 #1) id 18Y9Xr-00TBhH-00 for chemistry@ccl.net; Mon, 13 Jan 2003 13:42:47 -0500 Date: Mon, 13 Jan 2003 13:42:47 -0500 From: Mihaly Mezei X-X-Sender: mezei@fulcrum.physbio.mssm.edu To: Computationl Chemistry List Subject: water molecules Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Sender: Mihaly Mezei The most general way of finding out where the waters like to be is simulations in the grand-canonical ensemble. Such a work is described at http://inka.mssm.edu/~mezei/proj/br/ and references therein, including the software used (http://inka.mssm.edu/~mezei/mmc). Mihaly Mezei, Dept. of Physiology & Biophysics, Mount Sinai School of Medicine Voice: (212) 241-2186 Fax: (212) 860-3369| WWW (MSSM home): http:// adsr13.mssm.edu/domains/dept/facultyInfo.epl?objname=physbio&user=mezeim01 WWW (Lab home - software, publications): http://inka.mssm.edu/~mezei From chemistry-request@server.ccl.net Mon Jan 13 17:27:25 2003 Received: from cholla.wustl.edu ([128.252.62.53]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DMRP412415 for ; Mon, 13 Jan 2003 17:27:25 -0500 Received: (from baker@localhost) by cholla.wustl.edu (8.11.6/8.11.6) id h0DMR0X05994; Mon, 13 Jan 2003 16:27:00 -0600 Date: Mon, 13 Jan 2003 16:27:00 -0600 From: "Nathan A. Baker" To: Andreas Svrcek-Seiler Cc: Vlad Cojocaru , amber , CCL Subject: Re: CCL:electrostatic potential calculations Message-ID: <20030113162700.B5947@cholla.wustl.edu> Reply-To: Nathan Baker References: <3E2040B3.4070605@mpi-bpc.mpg.de> Mime-Version: 1.0 Content-Type: text/plain; charset=us-ascii Content-Disposition: inline User-Agent: Mutt/1.2.5.1i In-Reply-To: ; from svrci@tbi.univie.ac.at on Sat, Jan 11, 2003 at 05:43:33PM +0100 Organization: Washington University in St. Louis X-URL: http://www.biochem.wustl.edu/~baker Thanks for the plug! APBS is nominally in beta (to allow me to cover my rear when folks find bugs) but has been reasonably stable for several months now. It's also free and very portable. Please check it out (http://agave.wustl.edu/apbs)! Andreas Svrcek-Seiler (01-11-2003 17:43:33+0100): >Hi, > >> Does anyone know a freeware for calculating the electrostatic potential >> distribution on macromolecule (something like DelPHI). As far as I know >>...yes, MEAD is free (get it from >ftp://ftp.scripps.edu/pub/electrostatics/ >) >->cool program suite, very flexible, easy to use and fortran-free (!), >but sparsely documented. >an alternative might be apbs >( go to http://agave.wustl.edu/apbs/), >which is still beta but looks promising (I've compiled >but not really tried it). > >I hope that helps, >good luck >Andreas > > > >-- > > ))))) > ((((( > ( O O ) >-------oOOO--(_)--OOOo----------------------------------------------------- > o Wolfgang Andreas Svrcek-Seiler > o (godzilla) > svrci@tbi.univie.ac.at > .oooO Tel.:01-4277-52733 > ( ) Oooo. >-------\ (----( )-------------------------------------------------------- > \_) ) / > (_/ > > > >-= This is automatically added to each message by mailing script =- >CHEMISTRY@ccl.net -- To Everybody | CHEMISTRY-REQUEST@ccl.net -- To Admins >Ftp: ftp.ccl.net | WWW: http://www.ccl.net/chemistry/ | Jan: jkl@ccl.net > > > > End of message from Andreas Svrcek-Seiler. -- Nathan A. Baker, Assistant Professor Washington University in St. Louis School of Medicine Dept. of Biochemistry and Molecular Biophysics Center for Computational Biology 700 S. Euclid Ave., Campus Box 8036, St. Louis, MO 63110 Phone: (314) 362-2040, Fax: (314) 362-0234 URL: http://www.biochem.wustl.edu/~baker From chemistry-request@server.ccl.net Mon Jan 13 15:32:22 2003 Received: from yellow.csi.cam.ac.uk ([131.111.8.67]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0DKWL410595 for ; Mon, 13 Jan 2003 15:32:21 -0500 Received: from atg21 (helo=localhost) by yellow.csi.cam.ac.uk with local-esmtp (Exim 4.10) id 18YBFs-0002jF-00; Mon, 13 Jan 2003 20:32:20 +0000 Date: Mon, 13 Jan 2003 20:32:20 +0000 (GMT) From: Alfonso Garcia Sosa X-X-Sender: atg21@yellow.csi.cam.ac.uk To: Lucilla Angeli cc: chemistry@ccl.net Subject: Re: CCL:Water molecules In-Reply-To: <3E22EC5C.B47DC6B2@student.unisi.it> Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear Lucilla My belief is that some water molecules that appear in the same locations in different structure determinations of an enzyme are important and should be included in docking studies. Their inclusion can improve the accuracy of the predicted binding energy, as well as alter the geometrical and physycochemical properties of the active site. Several factors can help to determine if a water molecule is important and should be considered "bound" to the protein surface. The Journal of Molecular Modeling has recently accepted a paper in which we describe how it is possible to score water molecules based on simple structural values and to calculate a probability value of them remaining bound. I can provide you with more specific details if you would like. -- Alfonso Garcia-Sosa atg21@cam.ac.uk Tel (44) 1223 238042 http://www.cus.cam.ac.uk/~atg21 Drug Design Group, Dept. of Pharmacology, University of Cambridge & De Novo Pharmaceuticals, Histon, Cambridge, UK. On Mon, 13 Jan 2003, Lucilla Angeli wrote: > Dear CCLers > I have to do a docking study of some inhibitors of an enzyme, but I > don't know what to do with the water molecules. > Could you suggest to me a general method to handle these water molecules > found in the crystal structure (PDB) of enzymes? > Have I to consider them in my simulations? > Or, have I to ignore them? > Could you advise any papers about this argument? > I'll be grateful for any suggestion. > Lucilla > > -- > > ********************************* > Lucilla Angeli > c/o Prof. Botta > Dip. Farmaco Chimico Tecnologico > Universita' degli Studi Di Siena > Via Aldo Moro > I-53100 Siena, Italy > Phone: ++39 0577 234307 > Fax: ++39 0577 234333 > ********************************** > > > From chemistry-request@server.ccl.net Mon Jan 13 21:41:46 2003 Received: from ns0.scripps.edu ([192.42.82.58]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id h0E2fj417998 for ; Mon, 13 Jan 2003 21:41:45 -0500 Received: from antigen.scripps.edu (antigen.scripps.edu [137.131.200.100]) by ns0.scripps.edu (8.11.6/TSRI-4.1rx) with SMTP id h0E2fj822308 for ; Mon, 13 Jan 2003 18:41:45 -0800 (PST) Received: from relay2.scripps.edu(137.131.200.30) by antigen.scripps.edu via csmap id 4085; Mon, 13 Jan 2003 18:36:02 -0800 (PST) Received: from goliath.scripps.edu (goliath.scripps.edu [137.131.108.88]) by relay2.scripps.edu (8.11.6/TSRI-4.2rAV) with ESMTP id h0E2fXC21511; Mon, 13 Jan 2003 18:41:33 -0800 (PST) Received: from goliath (goliath [137.131.108.88]) by goliath.scripps.edu (SGI-8.9.3/TSRI-3.0.1) with ESMTP id SAA08673; Mon, 13 Jan 2003 18:41:33 -0800 (PST) Date: Mon, 13 Jan 2003 18:41:32 -0800 From: "Garrett M. Morris" To: Robert Flight cc: Computational Chemistry List , Lucilla Angeli Subject: Re: CCL:Water molecules In-Reply-To: <3E2846F2@webmail1> Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear Robert and Lucilla, You posed an interesting question, Lucilla, one that comes up all the time in docking. I would point out, though, that you have always been able to model waters in AutoDock explicitly, and I often recommend docking to a protein with and without the key waters, to determine what impact they might have on the dockings. For example, take a look at: Osterberg, F. et al. (2002) "Automated Docking to Multiple Target Structures: Incorporation of Protein Mobility and Structural Water Heterogeneity in AutoDock", Proteins, 46:34-40. You could use Consolv to help determine which waters you should keep as part of the protein and thus be included into the grid maps. Garrett On Mon, 13 Jan 2003, Robert Flight wrote: > Dear Lucilla, > > Most docking programs available are used with the assumption that the docking > is done with the water molecules absent. Many docking programs includes an > implicit solvation function that tries to account for solvation affects of the > ligand and the receptor, but cannot account for any molecule specific > interactions such as water molecules that act as "bridges" between the ligand > and the receptor (an exception to this is a paper on FLEXX, Rarey, M. et al. > (1999) PROTEINS, vol 34, p 17-28). > > Depending on the enzyme system, individual water molecules may be very > important. If you have PDB files of the enzyme with various inhibitors with > the enzyme, I would try docking with and without the water molecules > included. If you dont have any files like this, there are some options > reported in the literature. > > GRID - can be used to look at potential water sites in the receptor (Goodford, > P.J. (1985) J. Med. Chem., vol 28, 849-857 and Minke, W.E. et al. (1999) J. > Med. Chem., vol 42, p 1778-1788) > > Consolv - tries to predict which waters in the receptor will be displaced upon > ligand binding (Raymer, M.L. et al. (1997) J. Mol. Biol. vol 265, p 445-464, > also see http://www.bch.msu.edu/labs/kuhn/web/docs/consolv_doc.html) > > You can find a lot more by searching for water and docking in any decent > literature database. I havent found anything about a "general" method to > handle water molecules in the ligand that will work for all purposes. Good > luck with your study. > > Cheers, > > Robert > > >===== Original Message From Lucilla Angeli ===== > >Dear CCLers > >I have to do a docking study of some inhibitors of an enzyme, but I > >don't know what to do with the water molecules. > >Could you suggest to me a general method to handle these water molecules > >found in the crystal structure (PDB) of enzymes? > >Have I to consider them in my simulations? > >Or, have I to ignore them? > >Could you advise any papers about this argument? > >I'll be grateful for any suggestion. > >Lucilla > > > >-- > > > >********************************* > >Lucilla Angeli > >c/o Prof. Botta > >Dip. Farmaco Chimico Tecnologico > >Universita' degli Studi Di Siena > >Via Aldo Moro > >I-53100 Siena, Italy > >Phone: ++39 0577 234307 > >Fax: ++39 0577 234333 > >********************************** > > ******************************** > Robert Flight > Masters Student > Department of Chemistry > University of New Brunswick > Fredericton, NB Canada E3B 6E2 > e-mail: robert.flight@unb.ca > > ******************************** > > "A computer terminal is not some clunky old television with a > typewriter in front of it. It is an interface where the mind and > body can connect with the universe and move bits of it about." -- > Hitch Hikers Guide to the Galaxy > > > > -= This is automatically added to each message by mailing script =- > CHEMISTRY@ccl.net -- To Everybody | CHEMISTRY-REQUEST@ccl.net -- To Admins > Ftp: ftp.ccl.net | WWW: http://www.ccl.net/chemistry/ | Jan: jkl@ccl.net ___ Dr Garrett M. Morris, MA, DPhil The Scripps Research Institute, tel: (858) 784-2292 Dept. Molecular Biology, MB-5, fax: (858) 784-2860 10550 North Torrey Pines Road, email: garrett@scripps.edu La Jolla, CA 92037-1000, USA. www.scripps.edu/pub/olson-web/gmm