Abstract
Fifteen KSP inhibitors were docked into the receptor and the binding mode was analyzed for the first time. It was considered that in addition to the main binding pocket all the inhibitors merged in, there exists a cooperative minor binding pocket, which could be explored for significantly increased binding affinity. In addition, a good linear relationship between the biological activities and the lowest binding free energies has also been found. This may help in predicting the binding affinity of newly designed KSP inhibitors.
Two binding pockets considered after the analysis. Seven docked ligands (compound 1–7) were overlapped at the binding site. All inhibitors tested interacted with the main pocket, while CK0106023, interacted also with the cooperative minor pocket mainly surrounded by Arg221 and Ala218. Coloring of the binding site surface are different ends of each amino acid residue: blue represents amino group while red means carboxyl
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Acknowledgement
The authors thank Prof. Toshio Fujita from Kyoto University for comments to this paper. This work was financially supported by a grant from “The Six Top Talents” of Jiangsu Province (No. 06-C-023) and Specialized Research Fund for the Doctoral Program of Higher Education P.R.C. (No. 20060316006).
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Jiang, C., Chen, Y., Wang, X. et al. Docking studies on kinesin spindle protein inhibitors: an important cooperative ‘minor binding pocket’ which increases the binding affinity significantly. J Mol Model 13, 987–992 (2007). https://doi.org/10.1007/s00894-007-0219-2
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DOI: https://doi.org/10.1007/s00894-007-0219-2