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 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, 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 up the dominant adsorbed peptide conformations. Unlike REMD, however, ELM also 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 insight into the adsorbed peptide system provided sufficient care is taken to ensure key parts of the landscape are adequately sampled.

Advancing Rational Control of Peptide–Surface Complexes

“…Rational engineering of peptide assembly at surfaces is integral to the development of various applications of peptide–surface complexes such as, nanobiosensors, nanowires and novel biomimetic materials. − Key to achieving this goal is a control of both orientation and structure of the peptide in the adsorbed state. − To attain such control, a thorough understanding of the molecular interactions between peptides and surfaces is necessary. Graphene and related nanomaterials (GNM) have been of central interest as surfaces because of their excellent physiochemical and electrical properties. − Despite being considered as wonder materials, issues related to cytotoxic effects raised concerns and limited progress of their biological applications. − …”

Energy Landscapes of a Pair of Adsorbed Peptides

“…ELM was successful in locating a total of 1 223 837 minima and 1 116 410 saddle points. These numbers compare favorably with studies of comparable size and complexity, ,,− which typically report total numbers of stationary points in the order of 10 4 –10 6 . This database of stationary points will not be exhaustive owing to the complexity of the system: complete mapping of even a single adsorbed molecule has been noted as impractical, and the presence of a second molecule with additional degrees of freedom further exacerbates this, since the number of stationary points scales exponentially with the number of degrees of freedom .…”

“…In a previous study, the authors investigated a single met-enkephalin molecule above a flat, infinite graphite surface. This model is extended here to two met-enkephalin molecules (Tyr–Gly–Gly–Phe–Met), modeled using the CHARMM36m force field .…”

“…The ELM procedure applied here is similar to that used in the authors’ previous study . First, a basin-hopping procedure with simulated annealing (SA-BH) was used to build an extensive database of local potential energy (PE) minima.…”

“…Constructing large-scale connected databases of these minima and saddle points can yield information about the underlying potential energy and free energy surfaces, and detailed path information and rates can be obtained through discrete path sampling (DPS) . In recent work, the authors have demonstrated the applicability of ELM to a single adsorbed peptide. , Here, we demonstrate its application to two met-enkephalin peptides at a gas/graphite interface. The models, methodologies, and study details are outlined in Section .…”