Rationalizing tight ligand binding through cooperative interaction networks.

ABSTRACT: Small modifications of the molecular structure of a ligand sometimes cause strong gains in binding affinity to a protein target, rendering a weakly active chemical series suddenly attractive for further optimization. Our goal in this study is to better rationalize and predict the occurrence of such interaction hot-spots in receptor binding sites. To this end, we introduce two new concepts into the computational description of molecular recognition. First, we take a broader view of noncovalent interactions and describe protein-ligand binding with a comprehensive set of favorable and unfavorable contact types, including for example halogen bonding and orthogonal multipolar interactions. Second, we go beyond the commonly used pairwise additive treatment of atomic interactions and use a small

SUBMITTER: Kuhn B 

PROVIDER: S-EPMC3246350 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature