Conformational memories with variable bond angles.
Conformational Memories (CM) is a simulated annealing/Monte Carlo method that explores peptide and protein dihedral conformational space completely and efficiently, independent of the original conformation. Here we extend the CM method to include the variation of a randomly chosen bond angle, in addition to the standard variation of two or three randomly chosen dihedral angles, in each Monte Carlo trial of the CM exploratory and biased phases. We test the hypothesis that the inclusion of variable bond angles in CM leads to an improved sampling of conformational space. We compare the results with variable bond angles to CM with no bond angle variation for the following systems: (1) the pentapeptide Met-enkephalin, which is a standard test case for conformational search methods; (2) the proline ring pucker in a 17mer model peptide, (Ala)(8)Pro(Ala)(8); and (3) the conformations of the Ser 7.39 chi(1) in transmembrane helix 7 (TMH7) of the cannabinoid CB1 receptor, a 25-residue system. In each case, analysis of the CM results shows that the inclusion of variable bond angles results in sampling of regions of conformational space that are inaccessible to CM calculations with only variable dihedral angles, and/or a shift in conformational populations from those calculated when variable bond angles are not included. The incorporation of variable bond angles leads to an improved sampling of conformational space without loss of efficiency. Our examples show that this improved sampling leads to better exploration of biologically relevant conformations that have been experimentally validated.
Whitnell
Robert M
RM
Chemistry Department, Guilford College, Greensboro, North Carolina 27410, USA. rwhitnel@guilford.edu
Hurst
Dow P
DP
Reggio
Patricia H
PH
Guarnieri
Frank
F
D000465:Algorithms; D003198:Computer Simulation; D008954:Models, Biological; D009010:Monte Carlo Method; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013696:Temperature
D010455:Peptides; D011506:Proteins