Two dimensional umbrella sampling techniques for the computer simulation study of helical peptides at thermal equilibrium: The 3K(I) peptide in vacuoand solution

New computational techniques are developed to study conformational equilibr ium in helical peptides at finite temperature. Two dimensional umbrella sam pling methods involving coordinate systems which incorporate the cu-helical hydrogen bonding distances along the peptide backbone as collective variab les are presented. The umbrella sampling techniques are combined with new e xtended system multiple time step molecular dynamics simulation methods to allow peptide equilibria to be examined on a realistic potential energy sur face. In particular, this combination of methods is employed to study a six teen residue alanine-based peptide, Ac - (AAAAK)(3)A - NH2, at T = 300 K in vacuo and solution, under the all-atom CHARMM22 force field. The efficienc y of the multiple time step integration methodology permitted a minimum tot al run length of 30 ns to be employed in each umbrella sampling calculation reported. (C) 1998 American Institute of Physics; [S0021-9606(98)51948-4].