From chemistry-request@ccl.net Tue Jun 18 00:36:39 1991 From: Ralph Merkle To: chemistry@ccl.net Subject: MM2 size limits, request for information Date: Mon, 17 Jun 1991 19:47:06 PDT Status: R I've recently examined the Fortran source code for QCPE's MM2. The version I've examined can only handle 500 atoms. The constant 500 (and various other integer constants of mysterious purpose) are scattered throughout the code in array declarations, DO loop limits, statement labels, substrings of floating point numbers, and the like. Has anyone modified the QCPE code to parameterize the number of atoms it can handle? We're not sure how large a structure we'll want to handle, but more than 500 atoms is certain. Send any replys or information to: merkle@xerox.com From chemistry-request@ccl.net Tue Jun 18 01:22:18 1991 Date: Mon, 17 Jun 91 23:40:51 EDT From: states@ncbi.nlm.nih.gov (David States) To: chemistry@ccl.net Subject: Re: shake and potential functions Status: R Kim Sharp writes: 1) Missing terms in potential functions. Dave Pearlman's comments regarding the energy term implicit in the SHAKE constraint applies more generally in any constraint we add to potential functions. Another example is polarization: If we parameterize our force field to give a certain energy for some process where the polarization is in reality changing, but which our potential functions keep fixed, then we are implicitly putting energy in to maintain our constraint, but not including it in our final analysis of enegy changes... But polarization is not the only other place where this is a consideration. For example, atomic charge couples to bond length, bond angles, and dihedral angles (esp. in cases such as an amide bond where rotation couples to the hybridization). 2) If all SHAKE is giving you is a factor of 2, my personal feeling is that it is not worth the uncertainty involved if one is doing energy calculations. If it gave a factor of 10 maybe. In effect you are argueing that the uncertainties (errors?) introduced by SHAKE are the leading error in the potential function, but it is not at all clear to me that this is so. 3) Time and effort is probably better spent on treating electrostatic interactions in dynamics, since this is probably the most problematic area in dynamics. Maybe this is another area that will generate discussion. Again, agreed. Compared to the assumptions made in treating electrostatics, SHAKE seems pretty benign. Some issues: a) Cutoffs In effect aren't we doing very high salt strength simulations with a cutoff/Debye Huckle screening of long range effects? b) empirical dielectric functions: since there is no explicit h-bond potential, h-bonds are subsumed into the LJ and electrostatic terms. What happens when any other dielectric constant than e=1 is used (h-bonds are carefully parameterized in DISCOVER using a constant dielectric of one). Although DISCOVER allows one to use other constant and distant dependent dielectrics, do these have any meaning? Why do we uniformly neglect electronic polarization in calculating the dielectric constant for condensed phase simulations? In vacuo unity is appropriate, but in most condensed organic or bio-organic systems the index of refraction would suggest that electronic polarization (on a time scale fast compared to molecular vibration) is contributing a dielectric effect that is screening Coulombic interactions by a factor of two. If you assume that the numbers assigned to atomic charges bear any relationship to physical charge, then it would seem that this screening should be considered. Of course, if you actually do alter the dielectric constant, you will have to completely reparametrize all of the hydrogen bonding and many of the van der Waals interactions. Given the degree of coupling between these terms, one has to be very cautious in attaching physical meaning to them. After all, an empirical solvent model is in some sense just mathematical engine tuned to exhibit a set of behaviors we desire. c) neutralizing charged groups. this is standard procedure in NOE refinement. So long as we have enough NOE's/degree of freedom the system is determined enough that this seems to be o.k. Similarly, in nucleic acid simulations, it is common to scale the phosphate charges down to -0.2 to -0.3. It seems to "work", but is that justification enough. These approaches are pretty black box. what are people's experiences? I seem to recall that the long range rigidity of DNA can be predicted reasonably well based on polyelectrolyte theory alone. This would suggest that if you muck with the electrostatics and still see appropriate long range rigidity, then you have introduced a compensating error somewhere else. kim sharp, columbia u, dept of molecular biophysics David States National Center for Biotechnology Information/National Library of Medicine ----- End Included Message ----- From chemistry-request@ccl.net Tue Jun 18 14:34:44 1991 Date: Tue, 18 Jun 91 10:09:45 PLT From: 60847903@WSUVM1.CSC.WSU.EDU To: chemistry@ccl.net Status: R Hi netters, I am trying to develop a potential for Zinc atoms by the embedded at om method(EAM); this is to aid me in my research(which uses these potential tab les). If any of you has information on this could you just let me know? My e-ma il address is 60847903@wsuvm1.csc.wsu.edu Thanks. R. Ramprasad From chemistry-request@ccl.net Tue Jun 18 20:10:31 1991 Date: Wed, 19 Jun 91 09:16:01 +1000 From: apa@ccadfa.cc.adfa.oz.au (Alan P Arnold) To: chemistry@ccl.net Subject: Free-energy perturbation calcs of zinc<->peptide binding Status: R Hello to all AMBER gurus out there: I want to do a slow-growth free-energy perturbation calculation to estimate the Gibbs free-energy change for the process zinc-ion + peptide -> peptide. I have parameterised the zinc-ion in AMBER 3.0A as an 'H-bonding' type of atom ie. it has 10-12 well-depth and equilibrium bond distances with all relevent donor atoms on the peptide (peptide C=O, carboxylate-O, amine H2N's etc). In addition, it has a point-charge calculated by fitting the electrostatic potential with MOPAC. Thus the Zn<->donor atom interaction energy has two major sources (i) electrostatics and (ii) 10-12 well-depth. I have minimised the energy of this complex and intend to use the minimised structure as the start (LAMBDA=1) of the FEP simulation in which the zinc ion will be perturbed into a chargeless, sizeless dummy atom (LAMBDA=0). According to the documentation of GIBBS (FEP) in AMBER 3.0A, I should do this in two stages to decouple the electrostatic contribution to the perturbation energy. I am not clear on how I do this and would like some clarification: Am I right in thinking that I need to do 3 molecular dynamics simulations: (i) using MD to equilibrate the previously minimised structure to 298K - this may take 10ps or so with 1-2fs steps. Save the 'equilibrated' velocities and coords. (ii) start the GIBBS slow-growth using the equilibrated velocities and coords with IELPER=1 and vary LAMBDA from 1->0 over say, 20ps. (iii) start GIBBS again using the equilibrated velocities and coords with IELPER=-1 and again vary LAMBDA from 1->0 over the same interval. Is this procedure OK? How do I decide if 20ps was long enough? Do it again for 50ps from scratch? Any comments about the treatment of the zinc-ion <-> peptide binding ? Looking forward (I think) to some discussion .... ---- Alan Arnold | Phone: +61 62 68 8080 Chem. Department,University College | ACSNET: apa@ccadfa.oz Australian Defence Force Academy | UUCP: ...!seismo!munnari!ccadfa.oz!lpb CANBERRA ACT 2600 Australia | ARPA: apa%ccadfa.oz@SEISMO.CSS.GOV