Modeling and simulation of protein–surface interactions: achievements and challenges

Abstract

Abstract. Understanding protein-inorganic surface interactions is central to the rational design of new tools in biomaterial sciences, nanobiotechnology and nanomedicine. Although a significant amount of experimental research on protein adsorption onto solid substrates has been reported, many aspects of the recognition and interaction mechanisms of biomolecules and inorganic surfaces are still unclear. Theoretical modeling and simulations provide complementary approaches for experimental studies, and they have been applied for exploring protein-surface binding mechanisms, the determinants of binding specificity towards different surfaces, as well as the thermodynamics and kinetics of adsorption. Although the general computational approaches employed to study the dynamics of proteins and materials are similar, the models and force-fields (FFs) used for describing the physical properties and interactions of material surfaces and biological molecules differ. In particular, FF and water models designed for use in biomolecular simulations are often not directly transferable to surface simulations and vice versa. The adsorption events span a wide range of time-and length-scales that vary from nanoseconds to days, and from nanometers to micrometers, respectively, rendering the use of multi-scale approaches unavoidable. Further, changes in the atomic structure of material surfaces that can lead to surface reconstruction, and in the structure of proteins that can result in complete denaturation of the adsorbed molecules, can create many intermediate structural and energetic states that complicate sampling. In this review, we address the challenges posed to theoretical and computational methods in achieving accurate descriptions of the physical, chemical and mechanical properties of protein-surface systems. In this context, we discuss the applicability of different modeling and simulation techniques ranging from quantum mechanics through all-atom molecular mechanics to coarse-grained approaches. We examine uses of different sampling methods, as well as free energy calculations. Furthermore, we review computational studies of protein-surface interactions and discuss the successes and limitations of current approaches.

Controlling Redox Enzyme Orientation at Planar Electrodes

“…The electron entry or exit point will be the particular electronic relay on the surface of the enzyme that must be located at a close distance from the electrode (Figure 2). The molecular-level features favoring a specific orientation can be determined based on the examination of the crystallographic structure of the enzyme, possibly in combination with molecular modeling approaches [28]. Nevertheless, it is experimentally very difficult to succeed in a single-point attachment of an enzyme on an electrode surface.…”

“…Interestingly, the last decade has seen the development of numerous force fields (FF), specifically parameterized to model a large variety of solid surfaces [28]. Amongst the material models that are now accessible to computational chemists, one can mention metallic surfaces (Ag, Al, Au, Cu, Ni, Pb, Pd, Pt), for which Lennard-Jones potentials for nonbonded interactions have been developed [66].…”

“…To study functionalized electrode surfaces for enzyme immobilization, modeling approaches offer a window into the detailed surface interactions at the molecular level [28]. Several approaches can be used to predict the preferred orientation of enzymes on surfaces by modeling.…”

“…In their recent study on β-galactosidase grafted on a hydrophilic surface, Li et al used coarse-grain MD simulations to probe the enzyme orientation and its catalytic activity as a function of the surface's hydrophilicity [169]. Such coarse-grain approaches have been developed for modeling protein-surface interactions because they allow an increase in the time and length scales that are accessible during simulations [28]. While coarse-grain representations can successfully address issues such as proteins binding on surfaces [161], or folding [32], they are, however, unable to deal with oxido-reduction processes and could not be used to describe ET between surfaces and enzymes until now.…”

Bio- Medical Applications of Graphene, Its Modelling and Simulation

“…There are various factors which influence the study of nanocomposite such as size and shape of nanoparticle [25], crystal packing, defects, density of molecules and chemical state. MD technique is the most popular technique to be used for making biomedical computational study used by a number of researchers.…”