Energy landscape mapping and replica exchange molecular dynamics of an adsorbed peptide

Abstract

Adsorption of peptides at the interface between a fluid and a solid occurs widely in both nature and applications. Knowing the dominant conformations of adsorbed peptides and the energy barriers between them is of interest for a variety of reasons. Molecular dynamics (MD) simulation is a widely used technique that can yield such understanding. However, the complexity of the energy landscapes of adsorbed peptides means that comprehensive exploration of the energy landscape by MD simulation is challenging. An alternative approach is energy landscape mapping (ELM), which involves the location of stationary points on the potential energy surface, and its analysis to determine, for example, the pathways and energy barriers between them. In the study reported here, a comparison is made between this technique and replica exchange molecular dynamics (REMD) for met-enkephalin adsorbed at the interface between graphite and the gas phase: the first ever direct comparison of these techniques for adsorbed peptides. Both methods yield the dominant adsorbed peptide conformations. Unlike REMD, however, ELM readily allows the identification of the connectivity and energy barriers between the favored conformations, transition paths, and structures between these conformations and the impact of entropy. It also permits the calculation of the constant volume heat capacity although the accuracy of this is limited by the sampling of high-energy minima. Overall, compared to REMD, ELM provides additional insights into the adsorbed peptide system provided sufficient care is taken to ensure that key parts of the landscape are adequately sampled.