Modeling the free energy of polypeptides in different environments

An estimate of the free energy for increasing the content of helical and elongated backbone segments in polypeptides is given. Computer simulations of. "reasonable" random walks of isolated single chain all-atom models of a polypeptide are per-formed, and the potential energy of the obtained configurations is refined by using mean-field models for the molecular environment. The entropic contribution is computed assuming that entropy depends only on the enumeration of configurations (density of states) for each single chain. The free energy estimate is applied on several homo-polypeptides (X-40 with X = G, A, V, T, K, E) and to the A beta(1-40) peptide involved in Alzheimer's disease. Also, several peptides with the A beta(1-40) sequence randomly scrambled and the mini-protein villin headpiece HP(1-36) are analyzed.