Docking Server for the Identification of Heparin Binding Sites on Proteins
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- 作者：Scott E. Mottarella ; Dmitri Beglov ; Natalia Beglova ; Matthew A. Nugent ; Dima Kozakov ; Sandor Vajda
- 刊名：Journal of Chemical Information and Modeling
- 出版年：2014
- 出版时间：July 28, 2014
- 年：2014
- 卷：54
- 期：7
- 页码：2068-2078
- 全文大小：406K
- ISSN：1549-960X
文摘
Many proteins of widely differing functionality and structure are capable of binding heparin and heparan sulfate. Since crystallizing protein鈥揾eparin complexes for structure determination is generally difficult, computational docking can be a useful approach for understanding specific interactions. Previous studies used programs originally developed for docking small molecules to well-defined pockets, rather than for docking polysaccharides to highly charged shallow crevices that usually bind heparin. We have extended the program PIPER and the automated protein鈥損rotein docking server ClusPro to heparin docking. Using a molecular mechanics energy function for scoring and the fast Fourier transform correlation approach, the method generates and evaluates close to a billion poses of a heparin tetrasaccharide probe. The docked structures are clustered using pairwise root-mean-square deviations as the distance measure. It was shown that clustering of heparin molecules close to each other but having different orientations and selecting the clusters with the highest protein鈥搇igand contacts reliably predicts the heparin binding site. In addition, the centers of the five most populated clusters include structures close to the native orientation of the heparin. These structures can provide starting points for further refinement by methods that account for flexibility such as molecular dynamics. The heparin docking method is available as an advanced option of the ClusPro server at http://cluspro.bu.edu/.