Peptide Folding Problem: A Molecular Dynamics Study on Polyalanines Using Different Force Fields

In the last decade many advances have been made on molecular dynamics simulations and different force fields were developed from the combination of differentiable functions of the atomic coordinates to represent the system energy and of parameters that describe the geometric and energetic properties of inter-particle interactions. However, it has been shown that very subtle modifications to commonly used molecular mechanical potentials can significantly alter the behavior of those potentials inducing stabilizing or destabilizing effects in the patterns of peptides or proteins. In this article we describe the behavior of polyalanine peptides under the influence of various “force fields”. The polyalanines were chosen as study model since their structural features were already studied experimentally and thus our computational results were easily comparable with the experimental ones. In particular, three peptides composed of 8, 10 and 12 alanine residues were subjected to molecular dynamics simulations using 12 different force fields to understand what is the most appropriate force field to properly simulate their folding. Our results showed that Amber99? is the best force field able to generate helical conformations in agreement with experimental data.