Hello gmx'ers, I've been developing new residue topologies for the OPLS FF. These are backbone-bound Cu-complexes, where the metal is coordinated directly to a deprotonated amide N-atom, such as is observed at the N-terminal end of serum albumin. Im getting reasonable results, but unfortunately reviewers seem to have had no end of complaints about the way we have represented these things, so I'm hoping some experts out there could offer some useful suggestions on how I might proceed with the modeling, or at least hint that I really am on the right track.
Here's our current procedure: 1. Starting geometry for backbone atoms and the metal centre from X'tal structure 2. Harmonic potentials for Cu-ligand bonds 3. Harmonic potential for the backbone atoms immediately around the metal centre (these are planar complexes) 4. 1-4 pairs list updated to include the copper 1-4 interactions in the models 5. CHELPG charges calculated using B3LYP/6-31G(d) from an optimized X'tal geometry of the metal coordination site (at that same level of theory) The main complaints of our models have been: (1) the CHELPG charges that come out of the calculations are too small and would favour hydrophobic-types of interactions. One reviewer seems to be suggesting we start out with ion-like charges on the metal and ligands and go from there. I don't really like this idea as it's not consistent with the way the charges are derived for OPLS. Also any other charge-derivation method would no longer be consistent with OPLS(!). Comparing the backbone and side chain charges I calculate with their related atoms in similar molecule fragments in the OPLS force field they differ by less than 5-10% in most cases, except those directly involved in metal-coordination (which is not unexpected). (2) putting a harmonic potential on backbone dihedrals about the metal centre makes these things too flat. I say: Since Cu binds into the backbone, it replaces an H-atom and therefore the dihedral angle from Cu across the backbone to the carbonyl O-atom is actually somewhere between 160-180 degrees, and without explicitly entering the local dihedral angles based on X'tal data the force field only has the Cu-ligand bonds and backbone angles holding it in place, but nothing else to define local coordination geometry and backbone orientation. Does anyone who has done CHELPG charge derivation have suggestions on the CHELPG charge comments above? I'm using a radius of 1.4 A. for Cu2+. The complexes are overall charge-neutral, and the CHELPG charge on Cu usually comes out to be between 0.6 to 0.8 for all of the related complexes I've calculated (I have data for more than 20 related species in various protonation states and with different amino acids). This apparently low charge density (instead of something closer to 2+) at Cu may be because it is bound by two formally anionic backbone amide N-atoms that are deprotonated. Also, I have recently run B3LYP/6-31G(d) geometry optimizations and frequency calculations for a large number of hydrated Cu2+ complexes with various ligands, and am using the force constants from the frequency calculations (in mDyne/Angstrom, scaled by 60230) in the harmonic bond potentials for the copper ligands. Does anyone know if it is reasonable to expect an appreciable change in the magnitude of the force constant that is calculated depending on the overall charge metal complexes (i.e. 1+, 2+, neutral, etc.)? Jake Pushie Ph.D. Candidate Structural Biology Research Group University of Calgary Calgary, AB CANADA _______________________________________________ gmx-users mailing list [email protected] http://www.gromacs.org/mailman/listinfo/gmx-users Please don't post (un)subscribe requests to the list. Use the www interface or send it to [EMAIL PROTECTED] Can't post? Read http://www.gromacs.org/mailing_lists/users.php
