MM-ISMSA: An Ultrafast and Accurate Scoring Function for Protein鈥揚rotein Docking

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• 作者：Javier Klett ; Alfonso N煤帽ez-Salgado ; Helena G. Dos Santos ; 脕lvaro Cort茅s-Cabrera ; Almudena Perona ; Rub茅n Gil-Redondo ; David Abia ; Federico Gago ; Antonio Morreale
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2012
• 出版时间：September 11, 2012
• 年：2012
• 卷：8
• 期：9
• 页码：3395-3408
• 全文大小：600K
• 年卷期：v.8,no.9(September 11, 2012)
• ISSN：1549-9626

文摘

An ultrafast and accurate scoring function for protein鈥損rotein docking is presented. It includes (1) a molecular mechanics (MM) part based on a 12鈥? Lennard-Jones potential; (2) an electrostatic component based on an implicit solvent model (ISM) with individual desolvation penalties for each partner in the protein鈥損rotein complex plus a hydrogen bonding term; and (3) a surface area (SA) contribution to account for the loss of water contacts upon protein鈥損rotein complex formation. The accuracy and performance of the scoring function, termed MM-ISMSA, have been assessed by (1) comparing the total binding energies, the electrostatic term, and its components (charge鈥揷harge and individual desolvation energies), as well as the per residue contributions, to results obtained with well-established methods such as APBSA or MM-PB(GB)SA for a set of 1242 decoy protein鈥損rotein complexes and (2) testing its ability to recognize the docking solution closest to the experimental structure as that providing the most favorable total binding energy. For this purpose, a test set consisting of 15 protein鈥損rotein complexes with known 3D structure mixed with 10 decoys for each complex was used. The correlation between the values afforded by MM-ISMSA and those from the other methods is quite remarkable (r² 0.9), and only 0.2鈥?.0 s (depending on the number of residues) are spent on a single calculation including an all vs all pairwise energy decomposition. On the other hand, MM-ISMSA correctly identifies the best docking solution as that closest to the experimental structure in 80% of the cases. Finally, MM-ISMSA can process molecular dynamics trajectories and reports the results as averaged values with their standard deviations. MM-ISMSA has been implemented as a plugin to the widely used molecular graphics program PyMOL, although it can also be executed in command-line mode. MM-ISMSA is distributed free of charge to nonprofit organizations.