Paper Citing NAMD - Abstract
Masetti, Matteo; Cavalli, Andrea; Recanatini, Maurizio; Gervasio, Francesco Luigi
Exploring Complex Protein-Ligand Recognition Mechanisms with Coarse Metadynamics
JOURNAL OF PHYSICAL CHEMISTRY B, 113:4807-4816, APR 9 2009
The metadynamics method has been shown to be a valuable tool to study the mechanism of molecular recognition in atomistic detail [Gervasio, F. L.; et al. J, Am. Chem. Soc. 2005, 127, 2600]. However, it requires an a priori knowledge of all slow degrees of freedom relevant to the docking/undocking mechanism. Here we investigate a combination of docking/clustering with metadynamics performed with a subset of the necessary degrees of freedom (coarse metadynamics), and show that it provides a full mechanistic insight on the protein-ligand docking mechanism. Moreover, the proposed protocol is able to clearly distinguish between crystallographic and noncrystallographic poses of protein-ligand complexes, and also to find the transition state of the full undocking mechanism, thus giving an indication on the binding free energy.
