Using Molecular Dynamics to Improve Molecular Docking

We have been developing an improved method of protein-ligand docking. In our study of an intrinsically disordered protein, SNAP25B, we discovered that docking on a single rigid protein structure alone does not give us complete information on how the protein-ligand pair would interact in vivo, since intrinsically disordered proteins can form multiple 3D structures. A docking-predicted binding pose on this rigid structure may not exist in vivo due to the tendency of the 3D structure of the protein to change under different conditions. However, running the protein through a molecular dynamics (MD) simulation and collecting multiple 3D protein structures gives information about how the protein structure changes in solution. Docking on these MD-derived 3D protein structures increases the probability of finding an accurate ligand binding position using molecular docking that matches in vivo interactions.