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J Chem Inf Model. 2014 Aug 25;54(8):2371-9. doi: 10.1021/ci500209e. Epub 2014 Jul 18.

AutoDock4(Zn): an improved AutoDock force field for small-molecule docking to zinc metalloproteins.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute , La Jolla, California 92037, United States.

Abstract

Zinc is present in a wide variety of proteins and is important in the metabolism of most organisms. Zinc metalloenzymes are therapeutically relevant targets in diseases such as cancer, heart disease, bacterial infection, and Alzheimer's disease. In most cases a drug molecule targeting such enzymes establishes an interaction that coordinates with the zinc ion. Thus, accurate prediction of the interaction of ligands with zinc is an important aspect of computational docking and virtual screening against zinc containing proteins. We have extended the AutoDock force field to include a specialized potential describing the interactions of zinc-coordinating ligands. This potential describes both the energetic and geometric components of the interaction. The new force field, named AutoDock4Zn, was calibrated on a data set of 292 crystal complexes containing zinc. Redocking experiments show that the force field provides significant improvement in performance in both free energy of binding estimation as well as in root-mean-square deviation from the crystal structure pose. The new force field has been implemented in AutoDock without modification to the source code.

PMID:
24931227
PMCID:
PMC4144784
DOI:
10.1021/ci500209e
[Indexed for MEDLINE]
Free PMC Article

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