From ragno@naxos.caspur.it Fri Jan 17 03:16:57 1997 Received: from mail.caspur.it for ragno@naxos.caspur.it by www.ccl.net (8.8.3/950822.1) id CAA05619; Fri, 17 Jan 1997 02:42:59 -0500 (EST) Received: from naxos.caspur.it (naxos.caspur.it [193.204.5.8]) by mail.caspur.it (8.8.4/8.8.4) with ESMTP id IAA23158; Fri, 17 Jan 1997 08:41:21 +0100 Received: from localhost (ragno@localhost) by naxos.caspur.it (8.8.4/8.8.4) with SMTP id IAA16009; Fri, 17 Jan 1997 08:41:20 +0100 (MET) Date: Fri, 17 Jan 1997 08:41:20 +0100 (MET) From: Gianluca Sbardella Reply-To: Gianluca Sbardella To: orgchem-l cc: "Thomas R. Harrer" , chemistry@www.ccl.net, ANCHODD , Multiple recipients of List , Structural NMR Mail List Subject: Is OrgChem still "alive" ??? Message-ID: MIME-Version: 1.0 Content-Type: TEXT/PLAIN; charset=US-ASCII Dear Netters, I'm sending this question to a few different mail lists: my apologies for any repetitiion!!! The question is this: Does anybody know if ORGCHEM (Organic Chemistry Mail List) IS STILL ALIVE? Thank you all in advance, Gianluca Sbardella *************************************************************** * * * Dr. Gianluca Sbardella E-mail: r.ragno@caspur.it * * Dip. Studi Farmaceutici * * Universita' "La Sapienza" Phone: 39-6-49913814 * * P.le A. Moro, 5 Fax: 39-6-491491 * * 00185 Roma * * ITALY * * * *************************************************************** From toukie@zui.unizh.ch Fri Jan 17 03:17:06 1997 Received: from zzmkgtw.zzmk.unizh.ch for toukie@zui.unizh.ch by www.ccl.net (8.8.3/950822.1) id CAA05538; Fri, 17 Jan 1997 02:23:07 -0500 (EST) Received: by zzmkgtw.zzmk.unizh.ch; (5.65v3.2/1.3/10May95) id AA25592; Fri, 17 Jan 1997 08:28:24 +0100 Message-Id: <1.5.4.32.19970117072435.00666974@zui.unizh.ch> X-Sender: toukie@zui.unizh.ch (Unverified) X-Mailer: Windows Eudora Light Version 1.5.4 (32) Mime-Version: 1.0 Content-Type: text/plain; charset="us-ascii" Date: Fri, 17 Jan 1997 08:24:35 +0100 To: chemistry@www.ccl.net From: "Hr. Dr. S. Shapiro" Subject: MOPAC 6.0 for Windows 95 Cc: toukie@zui.unizh.ch Dear Colleagues; A week or so ago I posted a query about difficulties I was experi- encing running a DOS version of MOPAC 6.0 in a DOS box under Windows 95. I received a very large variety of possible workarounds, and I thank all re- sponders for their kind interest in my problem. One responder suggested that there was no point worrying about run- ning a DOS version of MOPAC 6.0 under Windows 95 when a version of MOPAC 6.0 compiled for execution under Windows 95 was available for download from http://ufark12.chem.ufl.edu/victor/mopac/index.shtml This website contains two MOPAC 6.0 executables: one for up to 50 atoms (MOPAC50.ZIP) and one for up to 150 atoms (MOPAC150.ZIP). These .zip files were easy enough to download, but after repeated attempts I always received a message from WinZip that something was wrong with the files and that they couldn't be uncompressed. So my questions to CCL subscribers are as follows: (a) Has anyone successfully downloaded, uncompressed, and used either MOPAC150.ZIP or MOPAC50.ZIP? If so, I'd like to hear from you about your experiences with either or both of these programmes. (b) My efforts to contact the person who I believe actually compiled MOPAC 6.0 as a Win95 executable, Dr. Victor Lobanov, have proven unsuccessful; mail sent to either of his e-mail addresses (victor@ufark2.chem.ufl.edu or victor@ycnex.3dp.com) bounces back as undeliverable. Does anyone know how to contact Dr. Lobanov? Thanks in advance to all responders, (Dr.) S. Shapiro ZH toukie@zui.unizh.ch From Jeffrey.Nauss@UC.Edu Fri Jan 17 11:17:01 1997 Received: from blues.fd1.uc.edu for Jeffrey.Nauss@UC.Edu by www.ccl.net (8.8.3/950822.1) id LAA07864; Fri, 17 Jan 1997 11:06:21 -0500 (EST) Received: from beryllium.crs.uc.edu by UCBEH.SAN.UC.EDU (PMDF V5.0-7 #15949) id <01IEBFEZTK8SH129NS@UCBEH.SAN.UC.EDU>; Fri, 17 Jan 1997 10:57:50 -0500 (EST) Received: by beryllium.crs.uc.edu (951211.SGI.8.6.12.PATCH1042/940406.SGI.AUTO) id KAA05438; Fri, 17 Jan 1997 10:58:15 -0500 Date: Fri, 17 Jan 1997 10:58:13 -0500 From: Jeffrey.Nauss@UC.Edu (Jeffrey L. Nauss) Subject: Summary: Removing charges for an MD simulation To: DIBUG@sunsite.icm.edu.pl, chemistry@www.ccl.net Reply-to: Jeffrey.Nauss@UC.EDU Message-id: <9701171058.ZM5436@beryllium.crs.uc.edu> Organization: Dept. Chemistry, University of Cincinnati MIME-version: 1.0 X-Mailer: Z-Mail (3.2.2 10apr95 MediaMail) Content-type: text/plain; charset=us-ascii Content-transfer-encoding: 7BIT X-Zm-Priority: Low Recently, I sent out the following post: +++++++++++ BEGIN ORIGINAL MESSAGE ++++++++++++++++ One of the problems one has in MD simulations is that long runs must be performed to see anything significant, for example, and in my specific case, determination of NMR order parameters or conformational searches. Performing the run in explicit solvent with periodic boundary conditions is undoubtably the best way to perform the simulations. However, these simulations require large amounts of CPU time and disk space for the large history files. To get around these problems, people have run simulations in vacuo. This was done in the early days of MD simulations but with parameter sets that often took into account the absence of solvent. Furthermore, electrostatic screening was accomplished by using a distance dependent dielectric constant. Still, a continuing problem that I have found during an in vacuo run is the collapse of the molecule. Proteins will shrink (in terms of the radius of gyration) and side chains will fall onto the surface of the protein. Peptides often fold up into themselves. To some extent, this collapse is a result of coulmbic interactions that are not properly shielded. Ornstein's group tried to get around this problem by rendering acidic, basic, N-termini, and C-termini functional groups net neutral (JBSD vol 9, page 935 (1992)). It appeared to be somewhat successful. Has anyone tried MD simulations, particularly with small molecules like peptides and carbohydrates, with a similar approach? I am thinking perhaps of performing the simulation with the Coulombic interactions scaled down or even shut off. Of course, one must assume that the Coulombic interactions will not play a major role in the dynamics. How valid is that assumption will depend on the system studied, I would think. Comments will be appreciated. References will be even better. +++++++++++ END ORIGINAL MESSAGE ++++++++++++++++ There seems to be a fair of amount of thought on the subject. And there seems to be some good results with various techniques. At least enough for me to give it a try. Here is a summary of the responses. Thank you to all who responded. ======================================================================== From: bear@ellington.pharm.arizona.edu (Soaring Bear) Are you aware of the approach of using higher dielectric r? There's been a bit of literature on using 4 instead of 1. I could dig up some refs if you want. >Forgot to mention that. Do you have a ref or two for it? comparison in: J Biomolec Struct & Dynam 11:429-41 1993 nice discussion by Daggett/Kollman: Biopolymers 31:285-304 1991 Chemica Scripta 29a:205-15 1989 mathematic treatment by Ramachandran: Indian J Biochem 7:95-7 1970 ======================================================================== From: D.van.der.Spoel@chem.rug.NL A conservative answer, just use the solvent and save yourself a lot of trouble justifying simulations without solvent. You can do nanosecond simulations of a protein in water on a reasonable workstation, or even a Pentium Pro PC. If performance is crucial, check out the GROMACS software, it is probably the fastest MD code on workstations. http://rugmd0.chem.rug.nl/~gmx ======================================================================== From: Peter Grootenhuis I fully appreciate the problem you described with long MD runs. It inspired us to generate a CHARMm-based force field for carbohydrates (CHEAT95) in which the effect of solvent is implicitly included. We also performed several MD-runs and typically got good results. The references are: Grootenhuis & Haasnoot, Mol.Simul. 10 (1993) 75-95 and Kouwijzer & Grootenhuis, J. Phys. Chem 99 (1995) 13426-13436 The CHEAT95 force field is available at: http://www.msi.com/support/quanta/cheat95.html ======================================================================== From: John Liebeschuetz We've, in the past, carried out a number of in vacuo simulations of drug/DNA complexes. No counterions were included so we scaled the phosphate charges to -0.25 to simulate counterion shielding. This figure was rather ad hoc but seemed to give reasonable results. Some of the ligands examined were cationic. These were scaled to a charge of +0.5 over the whole molecule and again seemed to give good results. In most of these simulations we still had to restrain the DNA to stop it collapsing. The charges on the cationic ligand were originally ESP calculated in AM1. We could have just halved the charges on each atom but we wanted to maintain the charge differentials between electropositive and electronegative atoms. This was done by carrying out the AM1 calculation on the unprotonated and protonated species and then averaging the charges on each atom. The charge on the extra proton was just halved. > Have you a reference for this work? Not for cases where the charges were partially removed. I do have one however for a case where the DNA phosphates were made neutral. N.L.Fregeau, Y. Wang, R.T.Pon, W.A.Wylie & J.W.Lown, J. Amer. Chem. Soc., 117 (1995), 8917-8925. > Did you manipulate the partial charges on the atoms to arrive at this scaled > down value or did you scale all Coulombic interactions? for DNA, the charges on the DNA phosphate oxygens only were scaled down. The charge on each atom was reduced by a quantity proportional to the original negative charge. This method was used whether the group was to be partially or fully neutralised. The ligand was treated differently. When the ligand cationic charge was scaled according to the method I described, the net effect was to alter atomic charges in the vicinity of the cation centre only. ======================================================================== From: Pieter Stouten >Ornstein's group tried to get around this problem by rendering acidic, >basic, N-termini, and C-termini functional groups net neutral (JBSD >vol 9, page 935 (1992)). It appeared to be somewhat successful. > GROMOS has had a force field with net neutral groups for vacuum simulations at least since 1984 (when I started using it), but probably much longer. It definitely works better than full-blown charges. See e.g.: D.M.F. van Aalten, A. Amadei, R.P. Bywater, J.B.C. Findlay, H.J.C. Berendsen, C. Sander & P.F.W. Stouten, "A Comparison of Structural and Dynamic Properties of Different Simulation Methods Applied to SH3," Biophys. J. 70 (1996) 684-692. We also found that stochastic dynamics (SD, with friction and random "kicks") worked better than straight MD. We also tried a simplistic continuum solvation term described in: P.F.W. Stouten, C. Froemmel, H. Nakamura & C. Sander, "An Effective Solvation Term Based on Atomic Occupancies for Use in Protein Simulations," Mol. Simulation 10 (1993) 97-120. That method is computationally cheap (20-50% increase in CPU time with respect to vacuum simulations), did work well in BPTI simulations (in fact, when I redid the simulations and was more careful in generating the starting configuration the results were better even than published in the paper), but not so well in the SH3 simulations. ======================================================================== From: Mark D Shenderovich I have discussed similar problems with fellow molecular modelers working with peptides and proteins. I don't know a reference that compares different electrostatic approximations in a systematic way, but I can share with you results of our discussions and my own experience. Charged groups of peptides in water are hydrated and interact through a medium of a high dielectrics. Using charged states of terminal and side chain groups in vacuo tremendously overestimates their electrostatic interactions and causes the collapse you've described. The charged groups tend to form salt bridges or multi-H-bond networks. To my experience, a distance dependent dielectrics makes the situation even worse since it stronger punishes separation of opposite charges. You may try a continuum solvation model which would increase CPU time by a reasonable factor of 2-5 and will not require additional disk space. I don't know which software you use, but several commercial packages include a continuum solvation. Although most of these models are poorly parametrized for charged species, it is better than nothing. Second, it is always safer to use neutral form of ionizable groups, both in vacuo and with an "envelope" hydration models (i.e. those which do not calculate effective dielectric constants). If you prefer simulations in vacuo, use a higher dielectric constant (4 to 10) with neutral groups, or a distance dependent dielectric with a coefficient around 4.0. I cannot prove these numbers, they came from my and my colleagues' experience. Also, if possible with your software, use aliphatic hydrogen parameters for neutral COOH groups. This is recommended by people from Scheraga's group to avoid excessive H-bonding of carboxyl. Finally, for conformational searches related to NMR data I often use a continuum dielectric constant of the solvent (80 for water, 45 for DMSO) with charged ionizable groups. Of course, this reduces electrostatics for neutral groups inside the peptide/protein, but they ether don't play a major role in intramolecular interactions or not vary much from one conformation to another. ======================================================================== From: JAQ@XRAY.BMC.UU.SE I saw you ccl-posting. You might find the references J. Mol. Biol. (1985) 183: 461 and Biopolymers (1990) 30: 205 useful. We looked at some of the issues you mention there, and there may be some other useful references for you as well. ======================================================================== From: "Thomas M O'Connell" We recently published a study on the helix-coil transition for short peptides that may be of interest to you. In this study we ran dynamics/free energy simulations in vacuo with the dielectric constant set to 5, 25 and infinity (i.e. all charges turned off). This of course had definite effects on the thermodynamics of the peptide conformation and folding. The reference is : Wang, O'Connell, Tropsha and Hermans Biopolymers 39, 479 (1996) Also of interest is a study that came out a while ago from Bernie Brooks in which he ran some dynamics on BPTI (if I remember correctly) in which all charges were removed. I can't seem to find this in my files so you'll have to do a search, but not surprizingly the folded system was stable. ======================================================================== From: case@riscsm.scripps.EDU (David Case) We've thought a lot about doing this, but for some reason have never actually tried it....For peptides, some models of solvation effects almost perfectly cancel out the conformational dependence of the electrostatic term, i.e. the sum of the (gas-phase) electrostatic term and the solvation term is nearly constant as a function of conformations sampled during a solvated MD run. So it's certainly not a crazy idea. No references yet, but we have a couple of papers submitted on this subject. ======================================================================== -- Jeff Nauss *********************************************************************** * UU UU Jeffrey L. Nauss, PhD * * UU UU Director, Molecular Modeling Services * * UU UU Department of Chemistry * * UU UU CCCCCCC University of Cincinnati * * UU UU CCCCCCCC Cincinnati, OH 45221-0172 * * UUUU CC * * CC Telephone: 513-556-0148 Fax: 513-556-9239 * * CC * * CCCCCCCC e-mail: Jeffrey.Nauss@UC.Edu * * CCCCCCC URL http://www.che.uc.edu/~nauss * *********************************************************************** From morokuma@euch4e.chem.emory.edu Fri Jan 17 12:17:02 1997 Received: from euch4e.chem.emory.edu for morokuma@euch4e.chem.emory.edu by www.ccl.net (8.8.3/950822.1) id LAA08087; Fri, 17 Jan 1997 11:36:46 -0500 (EST) From: Received: by euch4e.chem.emory.edu (AIX 3.2/UCB 5.64/4.03) id AA28035; Fri, 17 Jan 1997 11:36:46 -0500 Message-Id: <9701171636.AA28035@euch4e.chem.emory.edu> Subject: Summer Undergarduate Research at Emory To: chemistry@www.ccl.net Date: Fri, 17 Jan 1997 11:36:45 -0500 (EST) X-Mailer: ELM [version 2.4 PL24] Mime-Version: 1.0 Content-Type: text/plain; charset=US-ASCII Content-Transfer-Encoding: 7bit UNDERGRADUATE SUMMER RESEARCH FELLOWSHIP PROGRAM In Computational Chemistry & Physics June 9-August 15, 1997 Cherry L. Emerson Center For Scientific Computation EMORY UNIVERSITY Atlanta, Georgia, USA OBJECTIVE Provide intensive research training in computational chemistry/physics including electronic structures, molecular dynamics and modeling; gain experience using an IBM SP2 supercomputer and IBM RS6000 workstations; all of which, will enhance the student's career development in computational chemistry and physics. Fellows will pursue individual research projects under the direction of faculty members associated with the Center. Lectures, seminars by faculty, and student seminars will supplement the research program. QUALIFICATONS Completion of junior undergraduate year with a major in chemistry or physics. Criteria used in determining fellowship will include college grades, relevant experience and interest, and letters of recommendation from faculty members. SPECIAL FOR THIS YEAR This summer will be exceptional, in that, the 9th International Congress of Quantum Chemistry, the most important international conference in quantum chemistry, will be held at the Emory Conference Center from June 9-14, 1997. The first week of the undergraduate program will be devoted to attending the Congress and getting aquainted with the frontiers in computational chemistry. APPLICATION DEADLINE March 31, 1997 STIPEND $3500/10 week program. Up to $300 towards travel expenses is available upon request. HOUSING Double room occupancy is available for approx. $15/night and would be deducted from stipend. WEB SITE More details of the Emerson Center and the Undergraduate Summer Research Fellowship Program in Computational Chemistry & Physics can be found at our web site: http://www.emerson.emory.edu/ TO APPLY, 1. Go to the web site above and get the necessary information and forms, 2. or contact: Professor Keiji Morokuma, Director Cherry L. Emerson Center for Scientific Computation Emory University 1515 Pierce Drive Atlanta, Georgia 30322 Phone: (404) 727-2380 Fax: (404) 727-6586 E-mail: clec@euch3g.chem.emory.edu Emory University is an equal opportunity/affirmative action employer From ccl@www.ccl.net Fri Jan 17 18:17:03 1997 Received: from bedrock.ccl.net for ccl@www.ccl.net by www.ccl.net (8.8.3/950822.1) id RAA11840; Fri, 17 Jan 1997 17:54:57 -0500 (EST) Received: from xray5.chem.louisville.edu for dew01@xray5.chem.louisville.edu by bedrock.ccl.net (8.8.3/950822.1) id RAA16183; Fri, 17 Jan 1997 17:54:57 -0500 (EST) Received: (from dew01@localhost) by xray5.chem.louisville.edu (950413.SGI.8.6.12/950213.SGI.AUTOCF) id RAA29101 for chemistry@ccl.net; Fri, 17 Jan 1997 17:58:35 -0500 Date: Fri, 17 Jan 1997 17:58:35 -0500 From: dew01@xray5.chem.louisville.edu (Donald E. Williams) Message-Id: <199701172258.RAA29101@xray5.chem.louisville.edu> Apparently-To: chemistry@ccl.net SOFTWARE AVAILABILITY ANNOUNCEMENT Pdm97, Least-Squares Fitting of the Molecular Electrostatic Potential With Net Atomic Charges and/or Multipoles Reliable net atomic charges/multipoles can be found by fitting the molecular electric potential with program pdm97. The program provides a choice of geodesic(1), Connolly(2), cubic(3), or user specified grid points for the electric potential. The program includes calculation of hyperbolic-restricted charge magnitudes(4). In addition to net atomic charges, the program also allows any combination of atomic dipoles/quadrupoles, bond dipoles, as well as the addition of lone pair electron sites if required. The program directly reads output files from Gaussian-92 and Gaussian-94 programs, and will accept edited input from any program which produces a molecular electric potential on a grid. Program pdm97 is the most complete and versatile software package available for this type of calculation. Molecular interactions occur during host-substrate docking, cluster, and crystal formation - whenever molecules associate with one another. The energy and geometry of molecular association is determined by the force field. As a component of the force field, an accurate set of net atomic charges is required. Or, if higher accuracy is needed, pdm97 can make extensions to the net atomic charge model in a variety of ways. A particularly useful feature of the program is the easy and transparent way in which fixed charges and charge dependency conditions are specified. By specifying appropriate charge dependencies (e.g., equal charges or equal sums of charges), chemical intuition can assist to produce charges which are transferable between related types of molecules or molecular ions. Hyperbolic- restricted charges are specifically designed to increase charge transferability. All charge calculation include a complete error treatment with standard deviations and correlations between variables. References (1) Spackman, M. A., "Potential Derived Charges Using a Geodesic Point Selection Scheme", J. Comput. Chem 1996, 17, 1-18 (2) Connolly, M. L., "Solvent-accessible Surfaces of Proteins and Nucleic Acids", Science 221, 709-713 (1983) (3) Williams, D. E., "Net Atomic Charge and Multipole Models for the Ab Initio Molecular Electric Potential", Rev. Comp. Chem. 1991, 2, 219-271. (4) Bayly, C. L.; Cieplak, P.; Cornell, W. D.; Kollman, P. A., "A Well-Behaved Electrostatic Potential Based Method Using Charge Restraints for Deriving Atomic Charges: The RESP Model", J. Phys. Chem. 1993, 97, 10269-10280. For further information contact Dr. Donald E. Williams, Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA. E-mail:dew01@xray5.chem.louisville.edu Tel:(502)852-5975 Fax:(502)852-8149