AutoDock4Zn: An Improved AutoDock Force Field for Small-Molecule Docking to Zinc Metalloproteins

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• 作者：Diogo Santos-Martins ; Stefano Forli ; Maria Jo茫o Ramos ; Arthur J. Olson
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2014
• 出版时间：August 25, 2014
• 年：2014
• 卷：54
• 期：8
• 页码：2371-2379
• 全文大小：482K
• ISSN：1549-960X

文摘

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鈥檚 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 AutoDock4b>Znb>, 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.