From KEMIREC@hassle.astra.se Tue Jun 15 11:23:00 1993 Date: Tue, 15 Jun 93 09:23 +0200 From: "Bob Carter, +46 31-7761621" Subject: Charges / The GRID program To: chemistry@ccl.net Message-Id: <1993Jun15.092308.34.000232D3@hassle.astra.se> From: HASSLE::KEMIREC "Bob Carter, +46 31-7761621" 6-JUN-1993 17:53:33.41 To: PETER, INTERNET::"chemistry@ccl.net" CC: KEMIREC Subj: Charges / the GRID program Dear Netters, There's been a lot of discussion about charges and force fields on the net in recent months. Even though we all know that charges are "fictitious" entities, they are extremely useful in making decently accurate empirical force field calculations. It is however important to remember that a given charge parameter set is only valid in the context of a given force field. This was vividly brought home to me (once again!) in a talk by Peter Goodford at the recent Molecular Graphics Society meeting in York: he succinctly summarized most of the factors that might need to be taken into consideration in developing a scheme for the rapid estimation of charges for force field calculations. For example, the effects of solvent, neighboring charges, conformations, anisotropic polarizabilities; the problem of choosing an appropriate cutoff distance; the problem of dealing with hydrogen bonds; and so on and on. The point is that force fields are intrinsically arbitrary, i.e. different force fields take into account different combinations of these factors / effects, and in different ways. This is also why it is not advisable to take charges from one force field for use in another. Peter Goodford's own force field, developed for use in the GRID program, is certainly one of the best available today for calculating intermolecular interactions. This force field includes rather carefully developed / parameterized functions to deal with hydrogen bonding. The program is probably well known to most of the people on this network, but just in case there is someone who doesn't know about it, I'll provide a brief description here. GRID was originally described as "A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules" in J. Med. Chem. 28, 849 (1985); the current suite of programs is sold by Molecular Discovery, Ltd, Oxford, England; Phone: +44- 993-830385; Fax: +44-993-830966. GRID provides quite reasonably accurate predictions of "energetically favorable binding sites", if you have a structure for the biomacromolecule of interest; in addition, one can also look at interactions "from the point of view of the ligand", so to speak--GRID is now capable of dealing with a very large variety of organic chemical structures. Currently, with the advent of so-called 3D-QSAR, the GRID force field is being widely used to calculate interaction energies with a suitable "probe molecule" at a large number of points in a 3D "grid" enclosing the molecule(s) of interest. Using an appropriate multivariate statistical technique (PLS), one may attempt to find correlations between the calculated interaction energies and, for example, biological activity. (This general approach is called CoMFA---"Comparative Molecular Field Analysis", invented by Dick Cramer (TRIPOS) and Svante Wold (Umetri, Sweden).) The GRID suite of programs includes a routine that writes an input file for multivariate analysis in the SIMCA system (Umetri, Sweden) or in a system called GOLPE (Clementi et al., U. of Perugia). GRID is quite easy to use, and since it is written in standard Fortran 77, it runs on just about "anything" that has a Fortran compiler. Input is in PDB-format, which unfortunately means different things to different people, but an auxiliary program called GRIN helps the user create appropriate input. Output from GRID can be prepared in formats suitable for display in a number of commercially available molecular modelling packages (SYBYL, QUANTA, BioStructure, Chem-X, Insight, etc.). ( For more info, contact Peter Goodford directly at Molecular Discovery.) Greetings and salutations Bob Carter kemirec@hassle.astra.se From EWING@JCVAXA.JCU.EDU Tue Jun 15 09:20:00 1993 Date: Tue, 15 Jun 1993 14:20 EST From: "DAVID W. EWING (216) 397-4742" Subject: Responses to restricted vs. unrestricted semi-empirical question To: chemistry@ccl.net Message-Id: <01GZES5U8MLS8Y4ZFP@jcvaxa> Here's a summary of the responses to my recent question concerning restricted vs. unrestricted methods for semi-empirical Hamiltonians. Thanks to all who responded! The question: We're looking at some systems with doublet spin states using MOPAC5. Our previous work on some of these systems using ab initio methods told us that some of the wavefunctions are significantly spin contaminated ( about 1.0). Question: should we stick to restricted MNDO, MINDO/3, etc. or is it "safe" to use the unrestricted methods? The question arises because we are seeing significantly different results restricted vs. unrestricted. Dave Ewing John Carroll University ewing@jcvaxa.jcu.edu The answers: From: IN%"fredvc@esvax.dnet.dupont.com" 12-JUN-1993 14:17:38.66 UHF calculations are attractive because of their (relative) simplicity. They are *PROBABLY* alright for a qualitative assessment, e.g., for ESR interpretations, as long as the spin contamination is relatively "low" (whatever that means!!). Things begin to get sticky when comparisons of differing structures/isomers/conformations are involved. (1) Is the level of spin contamination the same? (2) Is the source of the contamination (quartet, sextet, etc.) the same for all forms? Projection techniques can clean things up a lot. This raises questions of approach, however. Do we do a UHF and project at the end, or do a PHF projecting as we go? I prefer the latter, thouhg it is easier to get codes for the former. I would tend to come down on the side of RHF methods, just to avoid the potential problems & ambiguities mentioned above. From: IN%"SDUDIS%BMSUEM11.BITNET@FRMOP11.CNUSC.FR" "Doug Dudis, WPAFB" 14-JUN-1993 04:09:08.66 This sounds like a more general problem. Specifically, for the polyacetylene case (and it's oligomers, the all trans polyenes, at least for the larger ones) the UHF wavefunction gives an INCORRECT geometry (and hence other problems). The real geometry is dimerized (that is, has double and single bonds) whereas the UHF wavefunction has someimbalance in it which results in a non-alternate structure (all bonds equal). This has been analyzed in some detail in the lit., and sounds similar to the problem you are encountering. I apologize for not giving the references, but I am on sabbatical in Belgium at the moment and so don't have access to all my references. As I recall, several of the papers were in J. Chem. Phys. a few years back. From: IN%"rwoods@biop.ox.ac.uk" 14-JUN-1993 14:09:52.26 In response to Dave Ewings question regarding spin contamination in semiempirical wavefunction I would just like to mention that I ran into the same problem when I incorporated a finite perturbation routine into MOPAC6.0. In some spin systems, notably those involving unsaturated carbon-carbon bonds and those involving nitro groups I could not get SCF convergence with a UHF-wavefunction regardless of the Hamiltonian (AM1, PM3 etc.). An examination of the values of S^^2 indicated that the wavefunctions were converging slowly, but actually diverged when MOPAC automatically applied any of its built-in "convergers". These convergers are applied when certain criteria such as the number of SCF-cycles have been passed. When I altered the code so that the automatic use of convergers such as "PULAY" and "CAMP-KING" was avoided the SCF slowly converged. I have been told that spin contamination in NDDO methods is an accepted draw-back. I would be very interested to hear if anyone else has explored methods of correcting this problem. From: IN%"asnegb01@asncube.asc.edu" "Eric G. Bradford" 11-JUN-1993 11:54:47.91 My experience in the past has been that MOPAC UHF will also give contamination in . I suggest that you use RHF and its half-electron approach to handling orbitals which are not fully occupied. From: IN%"jstewart@fai.com" 11-JUN-1993 16:01:25.52 For electronic structure, stick with RHF. For energetics, the RHF method will give heats of formation a little higher than UHF. The difference is likely to be almost constant, so if you are after trends, UHF will do. From: IN%"AHOLDER@VAX1.UMKC.EDU" "Andy Holder" 11-JUN-1993 18:21:55.97 I would stick with the RHF/HE methods. Remember that when one has an open shell in RHF, Dewar's half-electron protocol is used, which is usually pretty reliable. The spin-contaminated wave- functions are not valid. An alternative is to do CI and elimiate the contamination prob- lem altogether. AMPAC has the best CI stuff in it. From: IN%"jan@si.fi.ameslab.gov" 11-JUN-1993 18:32:23.96 About a year ago we implemented many features of MOPAC into our ab initio code GAMESS. In addition we added some new features, among them high spin ROHF. Since ROHF is an eigenfunction of the spin operator you avoid the problem of spin contamination. GAMESS can be obtained by writing Dr. Mike Schmidt at mike@si.fi.ameslab.gov, and is free of charge. Hope this helps. From: IN%"zheng@violet.berkeley.edu" 11-JUN-1993 18:39:24.19 As you said that there are two ways to treat open-shell system, one is using Dewar's Half-Electron method which works fine for doublet radical but it's relatively slow. The second method is pople's UHF method. Although the wavefunction is contaminated, it does give realistic results as far as ESP is concerned. HE method will not give you negative electron density. If you are interested in energetics, HE is the method of chioce. In the UHF treatment electron correlation has been overcalculated, therefore the energetics may not be good. HE will fail for biradicals or triplet carbene. I usually use UHF when the value is not too far from the that of pure state since it's faster. So again it depends on what want to get from your calculations. Yajun Zheng From: IN%"zheng@violet.berkeley.edu" 12-JUN-1993 12:28:11.35 In my previous mail I did not say clearly that uhf method could give negative spin density. HE method will not. As far as triplet carbene is concerned, we found that the error in calcualated heat of formation is related to the exchange integral Kij. (Dewar and Zheng unpublished results) Yajun From rrk@iris3.chem.fsu.edu Tue Jun 15 17:20:40 1993 Date: Tue, 15 Jun 93 21:20:40 -0400 From: rrk@iris3.chem.fsu.edu (Randal R. Ketchem) Message-Id: <9306160120.AA21783@iris3.chem.fsu.edu> To: CHEMISTRY@ccl.net Subject: searching protein sequences Netters, I am looking for a method to search a protein database, such as EMBL, for a certain amino acid sequence. I am also interested in searching by amino acid stereochemistry, but that is not as important. Please mail suggestions to 'rrk@sb.fsu.edu' and I will summarize to the list. ----- Randal R. Ketchem Institute of Molecular Biophysics Florida State University Tallahassee, FL 32306-3015 904.644.7798 (voice), 904.644.8281 (FAX) rrk@sb.fsu.edu From HACR0002@VM.CIS.SMU.EDU Tue Jun 15 14:24:23 1993 Message-Id: <199306160124.AA27948@oscsunb.ccl.net> Date: Tue, 15 Jun 93 20:24:23 CST From: Bingze Wang Subject: MOPAC.6 migration on SGI INDIGO To: CHEMISTRY@ccl.net Dear netters: We're trying to port MOPAC 6 from a SUN 4/490 to an SGI Indigo. The program runs but the energies for molecules with more than one heavy atoms are screwed up. Anybody seen this before? Bingze Wang