Molecular Simulation of Protein-Surface Interactions


Protein-surface interactions are fundamentally important in a broad range of applications in biomedical engineering and biotechnology. The adsorption behavior of a protein is governed by the complex set of interactions between the atoms making up the protein, surface, and surrounding solution. Molecular simulation provides a means of theoretically viewing, studying, and understanding these types of interactions at the atomic level. However, as with any application, molecular simulation methods must be properly developed and applied if protein-surface interactions are to be accurately portrayed. This chapter provides an overview of the basics of molecular simulation with a focus on the simulation of protein-surface interactions using molecular dynamics. Important issues such as force field transferability, solvation effects, and statistical sampling are addressed, as well as directions for further development. Molecular simulation methods have the potential to greatly enhance our ability to understand protein–surface interactions, leading to improvements in biomaterials design to control cellular response and to improve the sensitivity of biosensors and other bioanalytical systems.


Molecular Dynamic Simulation Force Field Monte Carlo Molecular Simulation Molecular Dynamic Method 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations and Symbols


bond length


force field parameter: bond length at zero energy


classical mechanics


potential energy




force vector between atoms i and j


generalized Born


kinetic energy


Boltzmann’s constant


force field parameter: bond stretching stiffness


stiffness constant for an umbrella-sampling simulation


force field parameter: dihedral angle rotational stiffness


force field parameter: bond angle bending stiffness






Monte Carlo


molecular dynamics


molecular mechanics


number of degrees of freedom


number of constraints on the degrees of freedom


constant number of atoms, pressure, and temperature


constant number of atoms, volume, and temperature






probability of system to be in state i


partial charge


configurational partition function of the system


quantum mechanics


replica-exchange molecular dynamics


distance between atoms i and j


self-assembled monolayer




temperature intervals with global energy reassignment


temperature intervals with global exchange of replicas-2


name of a type of three-site water model


internal energy






coordinate position


biasing energy function between states i and j


time-step increment for a molecular dynamics simulation


force field parameter: rotational dihedral shift


relative dielectric constant


well-depth for Lennard–Jones interactions


permittivity of free space


bond angle


force field parameter: bond angle at zero energy


variable coordinate parameter for an umbrella-sampling simulation


fixed coordinate parameter for an umbrella-sampling simulation


collision diameter between atoms i and j ϕdihedral angle



I thank my colleague Dr. Steven Stuart, Department of Chemistry, Clemson University, for numerous helpful discussions over the years regarding molecular simulation and statistical thermodynamics, Mr. Galen Collier, a current doctoral student in my group for assistance with Fig. 4.5, and Dr. Feng Wang, a former doctoral student in my group, for helpful discussions regarding the protein-folding funnel and protein adsorption. I also thank the NIH and NSF for providing funding support for my research program on the development of molecular simulation methods to simulate protein-surface interactions: NIH R01 EB006163, R01 GM074511, the NJ Center for Biomaterials RESBIO (NIH, P41 EB001046), and the Center for Advanced Engineering Fibers and Films (CAEFF, NSF-ERC, EPS-0296165).


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of BioengineeringClemson UniversityClemsonUSA

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