Revisiting free energy calculations: a theoretical connection to MM/PBSA and direct calculation of the association free energy.

ABSTRACT: The prediction of absolute ligand-receptor binding affinities is essential in a wide range of biophysical queries, from the study of protein-protein interactions to structure-based drug design. End-point free energy methods, such as the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) model, have received much attention and widespread application in recent literature. These methods benefit from computational efficiency as only the initial and final states of the system are evaluated, yet there remains a need for strengthening their theoretical foundation. Here a clear connection between statistical thermodynamics and end-point free energy models is presented. The importance of the association free energy, arising from one molecule's loss of translational and rotational freedom

SUBMITTER: Swanson JM 

PROVIDER: S-EPMC1303837 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature