Flexibility of tripeptides in solution: free energy molecular mechanics

A full theory of the conformations of biopolymers requires a method for treating the effects of solvent on the induced structures. This is especially critical in aqueous solvent where hydrogen‐bonding and dielectric shielding play major roles in determining the relative stability of conformers. Calculations of peptide conformations on a free energy surface are contrasted with the traditional sort of calculations which employs a simple potential energy function (in vacuo). The method employs a pairwise decomposable free energy surface determined by approximate analytical statistical mechanical theory. Applications are presented for tripeptides of alanine and glycine in water. This method, with precomputed free energy functions, takes the same amount of time and effort as traditional molecular mechanics in vacuo.