From chemistry-request@server.ccl.net Thu Dec 5 08:38:45 2002 Received: from mailer.gwdg.de ([134.76.10.26]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5DciA26102 for ; Thu, 5 Dec 2002 08:38:45 -0500 Received: from vrlab03.mpibpc.gwdg.de ([134.76.211.99] helo=mpi-bpc.mpg.de) by mailer.gwdg.de with esmtp (Exim 3.33 #13) id 18JwDE-0007fN-00 for chemistry@ccl.net; Thu, 05 Dec 2002 14:38:44 +0100 Message-ID: <3DEF56A6.30309@mpi-bpc.mpg.de> Date: Thu, 05 Dec 2002 14:37:42 +0100 From: Vlad Cojocaru User-Agent: Mozilla/5.0 (X11; U; Linux i686; en-US; rv:1.0.1) Gecko/20020823 Netscape/7.0 X-Accept-Language: en-us, en, ro MIME-Version: 1.0 To: CCL Subject: software for creating restraints from a pdb file Content-Type: text/plain; charset=us-ascii; format=flowed Content-Transfer-Encoding: 7bit Dear CCLers, Does anyone have an idea about a software (free) that can create restraints file (DIANA type) from a pdb file?? Thanks a lot for any suggestions, vlad -- Vlad Cojocaru Max Planck Institute for Biophysical Chemistry Department: 060 Am Fassberg 11, 37077 Goettingen, Germany tel: ++49-551-201.1389 e-mail: Vlad.Cojocaru@mpi-bpc.mpg.de home tel: ++49-551-9963204 From chemistry-request@server.ccl.net Thu Dec 5 01:46:55 2002 Received: from eggs.anadys.anadyspharma.com ([65.219.0.91]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB56krA30830 for ; Thu, 5 Dec 2002 01:46:53 -0500 X-MimeOLE: Produced By Microsoft Exchange V6.0.5762.3 content-class: urn:content-classes:message MIME-Version: 1.0 Content-Type: text/plain; charset="iso-8859-1" Subject: RE: V3000 molfile format Date: Wed, 4 Dec 2002 22:46:52 -0800 Message-ID: X-MS-Has-Attach: X-MS-TNEF-Correlator: Thread-Topic: V3000 molfile format Thread-Index: AcKa+AmWkb0s+ZIyTva7rPnkqrqddwBDG5Qw From: "Alberto Gobbi" To: Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id gB56ktA30831 Hi Everybody, without wanting to be ofensive I would like to ask if you have really considered all the options before creating a new file structure to store structures. The V2000 molfile format is well established and handles most of the cases required so far. There are thousands of applications which can read and write molfiles which would need to be modified. As one of your customers I do not consider that you are really doing us a good service in creating a new proprietary format. Also XML is becoming the standard for persistently storing and transmitting any kind of information worldwide in all different kinds of areas. There are a lot of standard, open, well tested and robust applications and libraries to read write and check for consistency of xml files. There is even an open standard CML (http://www.xml-cml.org/) for storing chemical structures and data based on XML. XML is carefully designed to be both flexible and extensible. It's certainly more extensible and flexible than the V3000 format and would surely meet not just MDL's present needs but their future needs as well. So if you really think that there is a need for storing additional information I feel you would do your customers a better service in supporting CML instead of creating a new standard which will cause a lot of headaches to people who would like to exchange structures or simply import them into their applications. With best regards, Alberto =============================================== Alberto Gobbi Anadys Pharmaceuticals 9050 Camino Santa Fe San Diego CA, 92121 USA ----------------------------------------------- AGobbi@AnadysPharma.com Tel.: +1 858 530 3657 -----Original Message----- From: Keith Taylor [mailto:K.Taylor@mdl.com] Sent: Tuesday, December 03, 2002 8:24 AM To: Computational Chemistry List Subject: CCL:V3000 molfile format If you use molfiles to transport structure information between applications, you need to be aware that MDL is introducing an enhancement to its stereochemical representation and this has an impact on the format of the molfile. The enhanced stereochemical representation will require the use of V3000 format molfiles and your molfile readers and writers will need to be updated to handle this information. MDL publishes the molfile format and the latest version of the document (August 2002) can be downloaded from: http://www.mdl.com/downloads/ctfile/ctfile_subs.html -= 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 From chemistry-request@server.ccl.net Thu Dec 5 03:46:04 2002 Received: from solar.pharma.hr ([161.53.121.4]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB58k1A02236 for ; Thu, 5 Dec 2002 03:46:04 -0500 Received: from bf7 (localhost [127.0.0.1]) by solar.pharma.hr (Postfix) with SMTP id A6541C944F for ; Thu, 5 Dec 2002 09:39:19 +0100 (CET) Message-ID: <001901c29c3b$446ea2a0$b37935a1@pharma.hr> From: "vgomzi" To: Subject: p-orbital spin densities in Gaussian98 Date: Thu, 5 Dec 2002 09:49:48 +0100 MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_NextPart_000_0016_01C29C43.A600B000" X-Priority: 3 X-MSMail-Priority: Normal X-Mailer: Microsoft Outlook Express 5.00.2615.200 X-MimeOLE: Produced By Microsoft MimeOLE V5.00.2615.200 This is a multi-part message in MIME format. ------=_NextPart_000_0016_01C29C43.A600B000 Content-Type: text/plain; charset="iso-8859-2" Content-Transfer-Encoding: quoted-printable Dear CCLers, I've asked this same question the people at the Gaussian a few days ago = but haven't received any answer, so I tought I could try here also... Below is relevant part of my original question to help@gaussian.com.=20 Please send any information or comments regarding this issue to my = e-mail, and, if there is any interest, I will summarize. I'm sorry if the question is trivial and I do thank You for Your time. =20 Sincerely, Vjeran Gomzi, =20 | Faculty of Pharmacy and Biochemistry, =20 | A. Kovacica 1, =20 | 10000 Zagreb, CROATIA =20 | e-mail:vgomzi@pharma.hr ----- Original Message -----=20 From: vgomzi=20 To: help@gaussian.com=20 Sent: Monday, December 02, 2002 5:05 PM Subject: Q: s- and p-orbital spin densities Dear Sir/Ms, I'm doing ab-initio calculations of EPR spectroscopic parameters using = Gaussian 98 program. There are two questions regarding calculation of = spin density distribution that I could not find anwers to in either "G98 = manual" or "Exploring chemistry..." book: 1) What are Atomic-Atomic Spin Densities that are calculated in the = program and, which is more important, 2) Is it possible to calculate total spin density distribution (on = specific atoms) in s- and p- type orbitals. What I mean is that, = although I get contributions to different MOs (using Pop=3DFull) of = certain AOs, it would require quite an effort to sum all the = contributions the proper way. So I'm wandering if there is some sort of = Keyword (or combination of such) that would enable me to get something = like 'Total atomic spin densities' entry of G98 output, but separated to = show how much spin density on each atom is in orbitals of s- or = p-character.=20 ------=_NextPart_000_0016_01C29C43.A600B000 Content-Type: text/html; charset="iso-8859-2" Content-Transfer-Encoding: quoted-printable
Dear CCLers,
I've asked this same question the = people at the=20 Gaussian a few days ago but haven't received any answer, so I tought I = could try=20 here also...
Below is relevant part of my original = question to=20 help@gaussian.com. =
Please send any information or comments = regarding=20 this issue to my e-mail, and, if there is any interest, I will=20 summarize.
 
I'm sorry if the question is trivial = and I do thank=20 You for Your time.
 
Sincerely,
Vjeran Gomzi,
 
| Faculty of Pharmacy and=20 Biochemistry,   
| A. Kovacica=20 1,            = ;            =             &= nbsp;  
| 10000 Zagreb,=20 CROATIA           =             &= nbsp;=20
| e-mail:vgomzi@pharma.hr
 
 
----- Original Message -----=20
From: vgomzi =
Sent: Monday, December 02, 2002 5:05 PM
Subject: Q: s- and p-orbital spin densities

Dear Sir/Ms,
 
I'm doing ab-initio calculations of EPR = spectroscopic parameters using Gaussian 98 program. There are two = questions=20 regarding calculation of spin density distribution that I could not find = anwers=20 to in either "G98 manual" or "Exploring chemistry..." book:
1) What are Atomic-Atomic Spin = Densities that are=20 calculated in the program and, which is more important,
2) Is it possible to = calculate total spin=20 density distribution (on specific atoms) in s- and p- type orbitals. = What I mean=20 is that, although I get contributions to different MOs (using = Pop=3DFull) of=20 certain AOs, it would require quite an effort to sum all the = contributions the=20 proper way. So I'm wandering if there is some sort of Keyword (or = combination of=20 such) that would enable me to get something like 'Total atomic spin = densities'=20 entry of G98 output, but separated to show how much spin density on each = atom is=20 in orbitals of s- or p-character.
 
 
------=_NextPart_000_0016_01C29C43.A600B000-- From chemistry-request@server.ccl.net Thu Dec 5 13:38:13 2002 Received: from cornell.edu ([132.236.56.6]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5IcDA04646 for ; Thu, 5 Dec 2002 13:38:13 -0500 Received: from cornell.edu (lock.lassp.cornell.edu [128.84.241.198]) by cornell.edu (8.9.3/8.9.3) with ESMTP id NAA12844 for ; Thu, 5 Dec 2002 13:38:12 -0500 (EST) Sender: cc236@cornell.edu Message-ID: <3DEF9D14.EED103EF@cornell.edu> Date: Thu, 05 Dec 2002 13:38:12 -0500 From: Connie Chang X-Mailer: Mozilla 4.79 [en] (X11; U; Linux 2.4.18-10smp i686) X-Accept-Language: en MIME-Version: 1.0 To: chemistry@ccl.net Subject: G98W & Hessian units Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit Hi there -- Can someone tell me exactly what units the Hessian matrix given by Gaussian98 output is in? And what exactly I have to do (what constants, expressions, etc.) to obtain the frequencies? Right now, I can get the frequencies out by multiplying the sqrt(eigenvalues(Hessian)) by ~1450, but for the life of me, I can't figure out what collection of constants will produce this. Thanks in advance. Connie From chemistry-request@server.ccl.net Thu Dec 5 15:42:28 2002 Received: from gate-sl1.mdli.com ([208.200.221.2]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5KgRA09308 for ; Thu, 5 Dec 2002 15:42:27 -0500 Received: (from smap@localhost) by gate-sl1.mdli.com (8.8.8/8.8.8) id MAA27952 for ; Thu, 5 Dec 2002 12:42:25 -0800 (PST) Received: from puffin.mdli.com(172.16.1.12) by gate-sl1 via smap (V2.1) id xma027942; Thu, 5 Dec 02 12:42:20 -0800 Received: from exch-sl02.mdli.com by puffin.mdli.com (980427.SGI.8.8.8/BCH1.0) id MAA21209; Thu, 5 Dec 2002 12:42:19 -0800 (PST) Received: by exch-sl02.mdli.com with Internet Mail Service (5.5.2653.19) id ; Thu, 5 Dec 2002 12:42:20 -0800 Message-ID: From: Keith Taylor To: CHEMISTRY@ccl.net Subject: RE: V3000 molfile format Date: Thu, 5 Dec 2002 12:42:19 -0800 MIME-Version: 1.0 X-Mailer: Internet Mail Service (5.5.2653.19) Content-Type: text/plain; charset="iso-8859-1" The V3000 molfile format is not new. It was first published in 1995 and its first role was to remove the arbitrary atom and bond limits that are built into the V2000 format. Unfortunately the V2000 structure is very limiting and is not extensible. Large structure tend not to be distributed as molfiles and therefore there have been very few of them in circulation. MDL's enhanced stereochemistry introduces a number of new representation features that could only be fitted in the V3000 format. We expect that the enhanced stereochemical representation will have a noticeable impact on the number of V3000 format molfiles in circulation. The V2000 format has served us well and will continue to serve us for many years. We have no plans to desupport it in our products. Structures that can be totally represented in the V2000 will continue to be handled in a V2000 format file. A V3000 format will be triggered only if the structure contains features that cannot be represented in the V2000 format. MDL is researching chemical structure file formats. XML is part of that research and compatibility with CML is under consideration. XML formats are very verbose and this imposes a large overhead when it comes to parsing them. If you are dealing with a small number of structures this overhead is tolerable. It is, however, common in our user base to need to work on structure sets that contain 100,000+ entries. The overhead then becomes significant and a more compact representation is required. This is why applications that consume large numbers of structures tend to read and write SDfiles or concatenated SMILES strings. If anyone would like to engage in a more detailed discussion about this issue or anything else connected with chemical structure representation please contact me directly at k.taylor@mdl.com. -----Original Message----- From: Alberto Gobbi [mailto:agobbi@anadyspharma.com] Sent: Wednesday, December 04, 2002 10:47 PM To: CHEMISTRY@ccl.net Subject: CCL:V3000 molfile format Hi Everybody, without wanting to be ofensive I would like to ask if you have really considered all the options before creating a new file structure to store structures. The V2000 molfile format is well established and handles most of the cases required so far. There are thousands of applications which can read and write molfiles which would need to be modified. As one of your customers I do not consider that you are really doing us a good service in creating a new proprietary format. Also XML is becoming the standard for persistently storing and transmitting any kind of information worldwide in all different kinds of areas. There are a lot of standard, open, well tested and robust applications and libraries to read write and check for consistency of xml files. There is even an open standard CML (http://www.xml-cml.org/) for storing chemical structures and data based on XML. XML is carefully designed to be both flexible and extensible. It's certainly more extensible and flexible than the V3000 format and would surely meet not just MDL's present needs but their future needs as well. So if you really think that there is a need for storing additional information I feel you would do your customers a better service in supporting CML instead of creating a new standard which will cause a lot of headaches to people who would like to exchange structures or simply import them into their applications. With best regards, Alberto =============================================== Alberto Gobbi Anadys Pharmaceuticals 9050 Camino Santa Fe San Diego CA, 92121 USA ----------------------------------------------- AGobbi@AnadysPharma.com Tel.: +1 858 530 3657 -----Original Message----- From: Keith Taylor [mailto:K.Taylor@mdl.com] Sent: Tuesday, December 03, 2002 8:24 AM To: Computational Chemistry List Subject: CCL:V3000 molfile format If you use molfiles to transport structure information between applications, you need to be aware that MDL is introducing an enhancement to its stereochemical representation and this has an impact on the format of the molfile. The enhanced stereochemical representation will require the use of V3000 format molfiles and your molfile readers and writers will need to be updated to handle this information. MDL publishes the molfile format and the latest version of the document (August 2002) can be downloaded from: http://www.mdl.com/downloads/ctfile/ctfile_subs.html -= 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 From chemistry-request@server.ccl.net Thu Dec 5 10:06:35 2002 Received: from fepF.post.tele.dk ([195.41.46.135]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5F6ZA29228 for ; Thu, 5 Dec 2002 10:06:35 -0500 Received: from [10.20.30.121] ([62.242.210.146]) by fepF.post.tele.dk (InterMail vM.4.01.03.29 201-229-121-129-20011121) with ESMTP id <20021205150634.RNDN25101.fepF.post.tele.dk@[10.20.30.121]> for ; Thu, 5 Dec 2002 16:06:34 +0100 Subject: Maestro files From: Kenneth Geisshirt To: chemistry@ccl.net Content-Type: text/plain Organization: Message-Id: <1039097193.2804.37.camel@localhost.cortex.local> Mime-Version: 1.0 X-Mailer: Ximian Evolution 1.2.0 Date: 05 Dec 2002 15:06:34 +0100 Content-Transfer-Encoding: 7bit Hi everyone I have been looking at Maestro files (Schrodinger's frontend to MacroModel and others), and I would like to know where I can find a library to read the files (I found a C/Fortran library at ftp.schrodinger.com called MMIO - but it seems to read older versions only). My platform is Linux and programming language is either C, Perl or PHP. Thanks in advance Kenneth Geisshirt From chemistry-request@server.ccl.net Thu Dec 5 12:12:31 2002 Received: from md.huji.ac.il ([132.64.169.2]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5HCUA01630 for ; Thu, 5 Dec 2002 12:12:31 -0500 Received: from NottingHill (amiram10.md.huji.ac.il [132.64.165.145]) by md.huji.ac.il (8.12.2/8.12.2) with SMTP id gB5HCUdE1559615 for ; Thu, 5 Dec 2002 19:12:30 +0200 (IST) Message-ID: <003101c29c81$88fad790$91a54084@NottingHill> From: "Andrea Scaiewicz" To: Subject: Peptides Database Date: Thu, 5 Dec 2002 19:12:48 +0200 MIME-Version: 1.0 Content-Type: multipart/alternative; boundary="----=_NextPart_000_002E_01C29C92.4C6BD9D0" X-Priority: 3 X-MSMail-Priority: Normal X-Mailer: Microsoft Outlook Express 5.00.2919.6700 X-MimeOLE: Produced By Microsoft MimeOLE V5.00.2919.6700 This is a multi-part message in MIME format. ------=_NextPart_000_002E_01C29C92.4C6BD9D0 Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable hi to all, I am interested in biologically active peptides. Do you know any = relevant database? =20 thanks in advance Andrea Scaiewicz ------=_NextPart_000_002E_01C29C92.4C6BD9D0 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable
hi to all,
 
 
I am interested in  biologically = active=20 peptides. Do you know any relevant database? 
thanks in advance
 
 
Andrea Scaiewicz
 
------=_NextPart_000_002E_01C29C92.4C6BD9D0-- From chemistry-request@server.ccl.net Thu Dec 5 12:05:32 2002 Received: from antivirus2.its.rochester.edu ([128.151.57.53]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5H5VA01254 for ; Thu, 5 Dec 2002 12:05:31 -0500 Received: from antivirus2.its.rochester.edu (localhost [127.0.0.1]) by antivirus2.its.rochester.edu (8.12.4/8.12.4) with ESMTP id gB5H5V8a002558 for ; Thu, 5 Dec 2002 12:05:31 -0500 (EST) Received: from mail.rochester.edu (mail1.ats.rochester.edu [128.151.224.31]) by antivirus2.its.rochester.edu (8.12.4/8.12.4) with SMTP id gB5H5VDj002555 for ; Thu, 5 Dec 2002 12:05:31 -0500 (EST) Received: from frenkel.chem.rochester.edu (frenkel.chem.rochester.edu [128.151.195.84]) by mail.rochester.edu (8.12.4/8.12.1) with ESMTP id gB5H5SlX002226 for ; Thu, 5 Dec 2002 12:05:28 -0500 (EST) Content-Type: text/plain; charset="us-ascii" From: wei Reply-To: weiz@mail.rochester.edu Organization: university of rochester To: chemistry@ccl.net Subject: help about NAMD Date: Thu, 5 Dec 2002 12:03:37 -0500 User-Agent: KMail/1.4.1 MIME-Version: 1.0 Message-Id: <200212051203.37346.weiz@mail.rochester.edu> Content-Transfer-Encoding: 8bit X-MIME-Autoconverted: from quoted-printable to 8bit by server.ccl.net id gB5H5WA01255 Dear all: I want to use langevin piston method for pressure control in NAMD, my system is pretty big (about 40000 atoms), and following is part of my config file: ***************************************** #NPT ENSEMBLE #Langevin dynamics langevin on # do langevin dynamics langevinDamping 5 # damping coefficient (gamma) of 5/ps langevinTemp 300 # bath temperature langevinHydrogen no # don't couple langevin bath to hydrogens # pressure langevinPiston on langevinPistonTarget 1.01325 # in bar -> 1 atm langevinPistonPeriod 200 langevinPistonDecay 500 langevinPistonTemp 300 useGroupPressure yes *********************************************** however, in the output (following is part of it), the pressure seems to be oscillating and far from the value I want: ****************************************** PRESSURE: 1830 39.2187 61.488 84.0019 61.488 22.6415 -37.0633 84.0019 -37.0633 28.6089 GPRESSURE: 1830 111.13 24.1343 100.18 151.549 81.3152 -31.7188 52.9986 -64.2686 96.83 ENERGY: 1830 1389.1377 3961.1676 2096.5308 290.2453 -309817.7510 26803.1094 0.0000 0.0000 52417.3218 -222860.2384 297.0 166 30.1564(this is the PRESSURE) 96.4250(THIS IS THE GPRESSURE) 859153.1859 -6.8394 5.7249 PRESSURE: 1840 -44.1607 47.0822 87.6176 47.0822 -76.5632 24.8784 87.6176 24.8784 -194.227 GPRESSURE: 1840 -1.39699 73.4161 86.3096 -29.9097 5.18774 -1.7759 55.9111 70.4077 -115.03 ENERGY: 1840 1366.7693 3995.7682 2121.9492 287.2088 -309756.6577 26597.6246 0.0000 0.0000 52664.2251 -222723.1125 298.4 156 -104.9835(PRESSURE) -37.0798(GPRESSURE) 859352.4078 -38.0042 -26.2113 PRESSURE: 1850 -48.9295 -121.345 -97.5314 -121.345 -5.10953 1.36691 -97.5314 1.36691 -53.157 GPRESSURE: 1850 26.8483 -81.3571 -168 -136.568 60.8743 23.3167 -11.4935 3.17469 2.01779 ENERGY: 1850 1352.3590 3971.5419 2109.2767 275.2429 -309848.9843 26611.7573 0.0000 0.0000 52870.0527 -222658.7538 299.5 819 -35.7320(PRESSURE) 29.9135(GPRESSURE) 859526.6482 77.2794 86.5364 PRESSURE: 1860 -74.9924 -29.2823 -147.055 -29.2823 -19.9078 -54.584 -147.055 -54.584 -32.6857 GPRESSURE: 1860 -47.3372 -137.701 -39.9964 -16.3545 64.2436 -51.6532 -186.098 -63.648 34.1783 ENERGY: 1860 1339.4640 3951.2615 2125.0371 281.8235 -309492.9603 26603.1521 0.0000 0.0000 52572.2691 -222619.9530 297.8 946 -42.5286(PRESSURE) 17.0282(GPRESSURE) 859821.2625 -72.3357 -62.8715 PRESSURE: 1870 -48.2164 32.7097 -25.1422 32.7097 -19.5578 131.794 -25.1422 131.794 -189.691 GPRESSURE: 1870 11.8128 69.6595 -16.5929 -31.0603 76.9998 153.058 -13.5146 127.546 -159.561 ENERGY: 1870 1344.7610 3904.3724 2131.2803 269.7844 -309693.7496 26654.1780 0.0000 0.0000 52815.3178 -222574.0555 299.2 718 -85.8218(PRESSURE) -23.5829(GPRESSURE) 859448.0882 -28.7219 -18.5036 PRESSURE: 1880 67.7263 23.0021 -17.5189 23.0021 104.987 156.01 -17.5189 156.01 26.7902 GPRESSURE: 1880 143.967 15.3178 -29.5841 95.2529 157.447 154.077 39.7776 161.029 103.826 ENERGY: 1880 1395.4111 3907.9728 2130.2727 276.0293 -310295.4807 27081.3588 0.0000 0.0000 52955.0848 -222549.3513 300.0 637 66.5012(PRESSURE) 135.0799(GPRESSURE) 858427.5064 -6.3696 3.6605 ***************************************************8 can anybody give me some hint about it? best regards wei zhuang From chemistry-request@server.ccl.net Thu Dec 5 16:48:40 2002 Received: from mail.rpi.edu ([128.113.22.40]) by server.ccl.net (8.11.6/8.11.0) with ESMTP id gB5LmdA12117 for ; Thu, 5 Dec 2002 16:48:39 -0500 Received: from webmail.rpi.edu (webmail.rpi.edu [128.113.26.21]) by mail.rpi.edu (8.12.1/8.12.1) with ESMTP id gB5LmPnY264076; Thu, 5 Dec 2002 16:48:25 -0500 Message-Id: <200212052148.gB5LmPnY264076@mail.rpi.edu> Content-Type: text/plain Content-Disposition: inline To: chemistry@ccl.net, parthi.s@jubilantbiosys.com From: "Dr. N. SUKUMAR" Organization: Rensselaer Polytechnic Institute Cc: qsar_society@accelrys.com X-Originating-Ip: 128.113.135.209 Mime-Version: 1.0 Reply-To: "Dr. N. SUKUMAR" Date: Thu, 05 Dec 2002 16:48:25 EST X-Mailer: EMUmail 4.00 Subject: Re: CCL:Quantum Chemistry in Drug Design X-Scanned-By: MIMEDefang 2.3 (www dot roaringpenguin dot com slash mimedefang) The CPU bottleneck has certainly been a major factor, but I believe a second factor is the descriptors commonly employed in drug design. If all one uses in modeling are molecular-geometry-derived descriptors, atom counts, topological descriptors and electrostatic potentials, then it hardly seems worthwhile performing accurate quantum chemical computations, especially in view of the enormous computational overhead. Ab initio cmputations, however, can generate a lot more information at a fundamental level, derived from the molecular wavefunction or electron density distribution. There are a few research groups (ours among them) that have investigated the use of electron-density-derived descriptors in drug design. In the Transferable Atom Equivalents (TAE) method, first introduced by Curt Breneman, we employ besides electrostatic potentials, electronic kinetic energy densities, the Laplacian distribution introduced by Bader, Fukui's function and Politzer's local average ionization potential. The distributions of these electronic properties on the molecular van der Waals surface (binned as histograms or encoded as wavelets) are used as descriptors. These electron-density-derived descriptors have found success in a number of applications, especially when used in combination with other traditional descriptors. For small datasets of small molecules, electron-density-derived descriptors can be readily determined from ab initio computions, but for large pharmaceutical datasets and for macromolecules, these descriptors can still be computed from an atomic-fragment-based approach using the theory of Atoms In Molecules. This is done in our RECON program, which employs atomic descriptors computed at HF/6-31+G* level and is available for download from our website. Typical CPU timings for RECON on a 1.7GHz Intel Pentium under linux are about 90 sec.for a set of 25 proteins and 7.5 min.for a 42,689 molecule dataset from NCI -- comparable to times for computing topological descriptors. So I would have to say that for such applications, CPU is no longer a limiting factor. Our protein chromatography studies are published in Mazza, et al, Anal.Chem. 73, 5457-5461 (2001) and Song, et al, J.Chem.Inf.Comput.Sci. 42, 1347-1357 (2002), while the drug design applications are in various stages of going to press and in press. Dr. N. Sukumar http://www.drugmining.com/ Rensselaer Department of Chemistry On Sat, 30 Nov 2002 07:11:34 +0530 "Parthiban" wrote: > Dear Friends: > While several QSAR related techniques and methodologies are appearing in > drug > design Journals, very few talk about the more accurate quantum chemical > methods in drug design arena. > > * What are the bottlenecks for the quantum chemical methods to get into > the > area of drug design. > > * For small molecules QC methods plays greater role, but for handling > drug- > like molecules and handling several thousands of compounds, QC methods do > not > see the limelight (correct me if i am wrong). Is the CPU-intensiveness > alone > is the reason. Or is there any some conceptual gap in this. [ I hear > someone > saying CPU-intensive is the reason and one has to wait for months to get > results ] > > * Based on your experience/insight, can you think of some timeframe, say > 5 > years, 10 years down the line, Quantum chemical methods would play a > major > role in the area of lead identification/optimization, or would you > say "prediction of future is difficult!". > > I look forward to reading your views. Thanks. > > S. Parthiban > Jubilant Biosys Ltd. > http://www.jubilantbiosys.com > > >