Energy landscapes for adsorption of a protein-like HP chain as a function of native-state stability

Abstract

Dynamic Monte Carlo (DMC) simulations of the adsorption of simple protein-like chains are used to more clearly define the molecular basis for the dependence of adsorption thermodynamics on the stability of the unique lowest-energy “native state” conformation of the chain. Arai and Norde were among the first to show that proteins of low native-state stability strongly denature upon adsorption to weakly attractive sorbent surfaces, while relatively modest changes in conformation are observed in stable proteins under identical adsorption conditions. When the protein has a low native-state stability, favorable adsorption entropies are typically observed in such systems, leading to the general belief that the chain gains conformational entropy during adsorption through a net reduction in intramolecular interactions specific to the native-state structure. Analysis of energy landscapes generated from our DMC simulation results show that a net loss in specific intramolecular interactions can lead to a positive Δ ads S under certain adsorption conditions. However, the influence of chain conformation on Δ ads S is found to correlate more directly with the manner in which the unique states of the system are distributed among the energy levels available to the adsorbed chain. Δ ads S is found to tend toward a maximum for adsorption processes described by thermally averaged energy landscapes in which the energy levels carrying the highest Boltzmann weights have a high degree of conformational degeneracy. This condition is met when the average interaction energy between the chain and the sorbent equals that between two hydrophobic segments of the chain.