Modeling Structural Coordination and Ligand Binding in Zinc Proteins with a Polarizable Potential.

ABSTRACT: As the second most abundant cation in human body, zinc is vital for the structures and functions of many proteins. Zinc-containing matrix metalloproteinases (MMPs) have been widely investigated as potential drug targets in a range of diseases ranging from cardiovascular disorders to cancers. However, it remains a challenge in theoretical studies to treat zinc in proteins with classical mechanics. In this study, we examined Zn(2+) coordination with organic compounds and protein side chains using a polarizable atomic multipole based electrostatic model. We find that polarization effect plays a determining role in Zn(2+) coordination geometry in both matrix metalloproteinase (MMP) complexes and in zinc-finger proteins. In addition, the relative binding free energies of selected inhibitors bin

SUBMITTER: Zhang J 

PROVIDER: S-EPMC3383645 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature