Potential and Free Energy Surfaces of Adsorbed Peptides

Abstract

Peptide adsorption on solid surfaces is a common process that occurs in nanotechnology and biology, with applications in the formation of nanomaterials, biosensing and drug delivery, amongst many others. Peptide adsorption involves complex processes that are difficult to characterise experimentally. Computational approaches such as molecular dynamics (MD) are often employed to better understand biomolecular systems. However, the computationally demanding nature of such systems combined with the long characteristic timescales of peptide adsorption means MD is not well suited to its study with current computing capacities. An alternative computational approach to characterising the behaviour of atoms and molecules is mapping the potential energy surface (PES) – the molecular energy as a function of the positions of all atoms – by determining its local energy minima and saddle points, which represent stable configurations and transition states that lie between them. These minima and saddle points may be located using optimisation algorithms. Harmonic approximations yield information about transition rates between minima via saddle points as well as the free energy surface (FES). This methodology – which is referred to as ‘energy landscape mapping’ (ELM) hereafter – is able to characterise fast and slow processes equally, only being limited by the size and complexity of the system studied, and the applicability of the potential energy models used. In the past, it has largely been applied to atomic and molecular clusters, and to biomolecules. It has never been applied to adsorption of peptides or any other biomolecule. In three journal papers included in this thesis, this approach is for the first time applied to adsorbed peptides. Firstly, ELM was applied to polyalanine adsorbed on surfaces of varying interactions strengths. Results obtained were comparable results to those obtained in a prior study of the same system using an evolutionary algorithm. In the second paper, ELM was applied to met-enkephalin at a gas/graphite interface, and compared with a molecular simulation technique designed for accelerating the simulation of slow processes, replica exchange molecular dynamics (REMD). In the final paper, ELM was applied to two met-enkephalin molecules at a gas/graphite interface, introducing an additional level of complexity and a step towards practical application, given real peptide adsorption processes often occur en masse. In all of these studies, information about transitions between conformations, energy barriers, rates, and the nature of the overall PES and FES, all of which were previously unknown for the systems studied, was obtained by ELM. The work conducted here has demonstrated the applicability of ELM to peptide/surface systems. Future work may consist of applying ELM to other similar processes of practical importance, developing and validating potential energy models suitable for modelling interfacial systems, including the effect of solvents, and continual development of the methodology to accelerate calculations.