James A. Ross-Naylor

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.

The wide relevance of peptide adsorption in natural and synthetic contexts means it has attracted much attention. Molecular Dynamics (MD) simulation has been widely used in these endeavors. Much of this has focused on single peptides due to the computational effort required to capture the rare events that characterize their adsorption. This focus is, however, of limited practical relevance as in reality most systems of interest operate in the non-dilute regime where peptides will interact with other adsorbed peptides. As an alternative to MD simulation, we have used Energy Landscape Mapping (ELM) to investigate two met-enkephalin molecules adsorbed at a gas/graphite interface. Major conformations of the adsorbed peptides and the connecting transition states are elucidated along with the associated energy barriers and rates of exchange. The last of these makes clear that MD simulations are currently of limited use in probing the co-adsorption of two peptides, let alone more. Overall, this study represents a significant step towards characterizing peptide adsorption beyond the dilute limit.

Peptide adsorption occurs across technology, medicine, and nature. The functions of adsorbed peptides are related to their conformation. In the past, molecular simulation methods such as molecular dynamics have been used to determine key conformations of adsorbed peptides. However, the transitions between these conformations often occur too slowly to be modeled reliably by such methods. This means such transitions are less well understood. In the study reported here, discrete path sampling is used for the first time to study the potential energy surface of an adsorbed peptide (polyalanine) and the transition pathways between various stable adsorbed conformations that have been identified in prior work by two of the authors [ Mijajlovic , M. ; Biggs , M. J. J. Phys. Chem. C 2007 , 111 , 15839−15847]. Mechanisms for the switching of adsorbed polyalanine between the stable conformations are elucidated along with the energetics of these switches.