Assessing the influence of electrostatic schemes on molecular dynamics simulations of secondary structure forming peptides

Electrostatic interactions play a fundamental role in determining the structure and dynamics of biomolecules in solution. However the accurate representation of electrostatics in classical mechanics based simulation approaches such as molecular dynamics (MD) is a challenging task. Given the growing importance that MD simulation methods are taking on in the study of protein folding, protein stability and dynamics, and in structure prediction and design projects, it is important to evaluate the influence that different electrostatic schemes have on the results of MD simulations. In this paper we performed long timescale simulations (500 ns) of two peptides, beta3 and RN24 forming different secondary structures, using for each peptide four different electrostatic schemes (namely PME, reaction field correction, and cut-off schemes with and without neutralizing counterions) for a total of eight 500 ns long MD runs. The structural and conformational features of each peptide under the different conditions were evaluated in terms of the time dependence of the flexibility, secondary structure evolution, hydrogen-bonding patterns, and several other structural parameters. The degree of sampling for each simulation as a function of the electrostatic scheme was also critically evaluated. Our results suggest that, while in the case of the short peptide RN24 the performances of the four methods are comparable, PME and RF schemes perform better in maintaining the structure close to the native one for the beta-sheet peptide beta3, in which long range contacts are mostly responsible for the definition of the native structure.