3.14 Molecular Simulation Methods to Investigate Protein Adsorption Behavior at the Atomic Level

Although protein adsorption to biomaterial surfaces is widely recognized as being an important mediator of biological response, a molecular-level understanding of protein–surface interactions is still lacking. Molecular simulation provides a means to study and understand these types of processes at the molecular level. Before this potential can be realized, however, appropriate methods must first be developed to enable protein adsorption behavior to be accurately represented in a molecular simulation. This article begins with an overview of some of the fundamentals of protein adsorption. It then introduces the field of molecular simulation and covers a series of topics regarding how molecular simulations are performed, with specific focus on three of the most important issues for the simulation of protein adsorption behavior: force field parameterization, representation of solvent effects, and sampling of the molecular system. A summary is then presented regarding how these methods have been developed and applied to simulate protein–surface interactions over the past two decades. This is followed by a discussion of the key areas for the continued development of molecular simulation methods toward the goal of providing these methods as powerful tools to guide the design of biomaterial surfaces to control protein adsorption behavior for a broad range of applications in biomedical engineering and biotechnology.