Efficient Incorporation of Protein Flexibility and Dynamics into Molecular Docking Simulations

Flexibility and dynamics are protein characteristics that are essential for the process of molecular recognition. Conformational changes in the protein that are coupled to ligand binding are described by the biophysical models of induced fit and conformational selection. Different concepts that incorporate protein flexibility into protein-ligand docking within the context of these two models are reviewed. Several computational studies that discuss the validity and possible limitations of such approaches will be presented. Finally, different approaches that incorporate protein dynamics, e.g., configurational entropy, and solvation effects into docking will be highlighted.