Molecular Modeling and Molecular Dynamics Simulations of Membrane Transporter Proteins

In silico methods are increasingly being used to address problems of biological significance. In the realm of structural biology, computational approaches have been applied to modeling the three-dimensional (3D) conformation of proteins and other molecules whose structures have not been solved, to simulate dynamic functions of proteins (such as catalysis and transport) (1 –6 ), to study interactions between ligands and their receptors (docking) (7 –9 ), and to perform initial screens in drug discovery efforts (10 ,11 ). With recent advances that have increased the speed of computations (i.e., “faster chips”) and with greater sophistication of software programs, it is now possible to undertake computational projects related to protein structure and folding that would have been virtually impossible 5–10 yr ago. There are two areas where computational methods have provided significant new insights into protein structure, namely molecular modeling and molecular dynamics (MD) simulations. This chapter will describe the theory and methodology related to these procedures.