Novel method for probing the specificity binding profile of ligands: applications to HIV protease.

ABSTRACT: A detailed understanding of factors influencing the binding specificity of a ligand to a set of desirable targets and undesirable decoys is a key step in the design of potent and selective therapeutics. We have developed a general method for optimizing binding specificity in ligand-receptor complexes based on the theory of electrostatic charge optimization. This methodology can be used to tune the binding of a ligand to a panel of potential targets and decoys, along the continuum from narrow binding to only one partner to broad binding to the entire panel. Using HIV-1 protease as a model system, we probe specificity in three distinct ways. First, we probe interactions that could make the promiscuous protease inhibitor pepstatin more selective toward HIV-1 protease. Next, we study clinicall

SUBMITTER: Sherman W 

PROVIDER: S-EPMC3480184 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature