Molecular mechanics and all-electron fragment molecular orbital calculations on mutated polyglutamine peptides

We perform potential energy calculations on mutant polyglutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing molecular dynamics, and were analyzed by molecular mechanics and by all-electron fragment molecular orbital energy calculations. In order to make a comparison between the two sets of potential energies, we devised a means of computing molecular-mechanical analogues of the quantum-mechanical energies. Our results suggest that in accordance with a previous paper (VanSchouwen et al., submitted for publication [16]) the experimentally-observed inhibition of aggregation is due to localized, geometry-based effects on peptide structure, with little appreciable perturbation from longer-range non-bonded effects. (C) 2009 Elsevier B.V. All rights reserved.