Calculating Structures and Free Energies of Complex Molecules: Combining Molecular Mechanics and Continuum Models
Peter A. Kollman, Irina Massova, Carolina Reyes, Bernd Kuhn, Shuanghong Huo, Lillian T. Chong, Matthew Lee, Tai‐Sung Lee, Yong Duan, Wei Wang, Oreola Donini, Piotr Cieplak, Jaysharee Srinivasan, David A. Case, Thomas E. Cheatham
Abstract
A historical perspective on the application of molecular dynamics (MD) to biological macromolecules is presented. Recent developments combining state-of-the-art force fields with continuum solvation calculations have allowed us to reach the fourth era of MD applications in which one can often derive both accurate structure and accurate relative free energies from molecular dynamics trajectories. We illustrate such applications on nucleic acid duplexes, RNA hairpins, protein folding trajectories, and protein-ligand, protein-protein, and protein-nucleic acid interactions.