Alpha/3(10)-helix transitions in alpha-methylalanine homopeptides: conformational transition pathway and potential of mean force.

The conformational transition between the alpha- and 3(10)-helical states of alpha-methylalanine homopeptides is studied with molecular mechanics. Conformational transition pathways for Ace-(MeA)n-NMe with n = 7, 9, and 11 are obtained with the algorithms of Elber and co-workers [R. Czerminski & R. Elber (1990) International Journal of Quantum Chemistry, Vol. 24, pp. 167-186; A. Ulitsky & R. Elber (1990) Journal of Chemical Physics, Vol. 92, pp. 1510-1511]. The free energy surface, or potential of mean force, for the conformational transition of Ace-(MeA)9-NMe is calculated from molecular dynamics simulations, and a method is presented for the decomposition of the free energy surface into the constituent energetic and entropic terms, via the calculation of the required temperature derivatives in situ. For the AMBER/OPLS model employed here, the conformational transition pathways each contain a single 3(10)-helical-like transition state, and the transition state potential energy relative to the 3(10)-conformation is 3 kcal/mol, independent of peptide length. Entropic stabilization in the barrier region significantly lowers the activation free energies for the forward and reverse transitions from the estimates of the barrier heights based simply on potential energy alone.