| The results of computer simulation studies of CH3CO - (Ala) 3 - NHCH3 solvated in bulk computer water, solvated in computer water clusters and in vacuo (isolated model molecule) at T = 300K using modern computational methods are presented. Specifically, the conformational free energy surface of the peptide is calculated via umbrella sampling using the distance between the amide hydrogen of N-terminus blocking group and the esteric oxyen of C-terminus blocking group as the reaction coordinate. Comparisons are made between results obtained using the several different force fields, CHARMM22 (A. D. MacKerell Jr. et al., unpublished), CHARMM19 (B. Brooks et al. J. Comp. Chem. 4, 187, 1983) and AMBER95 (Cornell et al. J. Am. Chem. Soc. 117, 5179 1995). Contact is made with the early studies on this system under the conditions of constant temperature and volume using the CHARMM19 force field to model the interactions, a small system and spherical cutoff to treat the coulomb interactions (D. J. Tobias and C. L. Brooks III, Biochemistry 30, 6059–6070 1991).; The umbrella sampling techniques applied to the blocked tripeptide are extended to the 3K(I) peptide. In particular, new methods are employed to study this sixteen residue alanine-based peptide, Ac - ( AAAAK)3A - NH2, at T = 300K in vacuo and solution, under the all-atom CHARMM22 force field. In contrast to the previous case, two dimensional umbrella sampling methods involving coordinate systems which in corporate the α-helical hydrogen bonding distances along the peptide backbone as collective variables are presented. The novel two dimensional umbrella sampling techniques developed are further applied to 3K(I) and two poly-alanine peptides at T = 300K in vacuo and solution, under the all-atom CHARMM22 and AMBER95 force fields. In particular, the ensemble of important conformers on the empirical biomolecular force fields are presented for these polypeptides at finite temperature. Two peptides are simulated in water, [(Ala)16] +Cl− and [Ac - (AAAAK )3A - NH2] 3+3Cl− in order to compare M.D. results to calculations in vacuo. In vacuo, two poly-alanine and one lysine doped poly-alanine peptide, [(Ala)8]+, [( Ala)16]+, [Ac - ( AAAAK)3A - NH2]3+, are examined and results compared to recent experimental work in vacuo using drift tube techniques. |
