Long-range Electrostatic Interactions in Molecular Dynamics: An Endothelin-1 Case Study

Abstract

An extensive conformational search in explicit solvent was performed in order to compare the influence of different long-range electrostatic interaction treatments in molecular dynamics. The short peptide endothelin-1 was selected as the subject of molecular dynamics studies that started from both X-ray and NMR obtained structures. Electrostatic interactions were treated using two of the most common methods—residue-based cutoff and particle mesh Ewald (PME). Analyses of free energy calculations (MM-PBSA method used), secondary structure elements and hydrogen bonds were performed, and there suggested that there is no unambiguous conclusion about which of the two methods of long-range electrostatics treatment should be used in MD simulations in this case. The most reliable data was provided by a trajectory that started with the NMR structure and used the cutoff method to treat electrostatic interactions. This leads to a recommendation that the choice of electrostatics treatment should be made carefully and not automatically by choosing the PME method simply because it is the most widely used.