Insights into Ligand鈥揚rotein Binding from Local Mechanical Response

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• 作者：Jagdish Suresh Patel ; Davide Branduardi ; Matteo Masetti ; Walter Rocchia ; Andrea Cavalli
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2011
• 出版时间：October 11, 2011
• 年：2011
• 卷：7
• 期：10
• 页码：3368-3378
• 全文大小：1140K
• 年卷期：v.7,no.10(October 11, 2011)
• ISSN：1549-9626

文摘

Computational studies of ligand鈥損rotein binding are crucial for properly designing novel compounds of potential pharmacological interest. In this respect, researchers are increasingly interested in steered molecular dynamics for ligand鈥損rotein binding and unbinding studies. In particular, it has been suggested that analyzing the work profiles along the ligand鈥損rotein undocking paths could be fruitful. Here, we propose that small portions of work profiles, termed 鈥渓ocal mechanical responses鈥?of the system to a steering force, could serve as a universal measure for capturing relevant information about the system under investigation. Specifically, we first collected a high number of steering trajectories using two biological systems of increasing complexity (i.e., alanine dipeptide and (R)-roscovitine/CDK5 complex). Then, we devised a novel postprocessing tool to be applied to the local mechanical responses, to extract structural information related to the biological processes under investigation. Despite the out-of-equilibrium character of the trajectories, the analysis carried out on the work profiles provided pivotal information about the investigated biological processes. This could eventually be applied to drug design.