Bringing Clarity to the Prediction of Protein-Ligand Binding Free Energies via "Blurring"

ABSTRACT: We present a method to evaluate the free energies of ligand binding utilizing a Monte Carlo estimation of the configuration integrals concomitant with uncertainty quantification. Ensembles for integration are built through systematically perturbing an initial ligand conformation in a rigid binding pocket, which is optimized separately prior to incorporation of the ligand. We call the procedure producing the ensembles "blurring", and it is carried out using an in-house developed code. The Boltzmann factor contribution of each pose to the configuration integral is computed and from there the free energy is obtained. Potential function uncertainties are estimated using a fragment-based error propagation method. This method has been applied to a set of small aromatic ligands complexed with T4

SUBMITTER: Ucisik MN 

PROVIDER: S-EPMC4006398 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature