A machine learning approach for the prediction of protein surface loop flexibility

作者：Hwang Howook; Vreven Thom; Whitfield Troy W; Wiehe Kevin; Weng Zhiping^*

来源：Proteins: Structure, Function, and Genetics , 2011, 79(8): 2467-2474.

DOI：10.1002/prot.23070

• backbone
• flexibility
• loop
• SVM
• beta-factor
• Random Forest
• protein

Proteins often undergo conformational changes when binding to each other. A major fraction of backbone conformational changes involves motion on the protein surface, particularly in loops. Accounting for the motion of protein surface loops represents a challenge for protein-protein docking algorithms. A first step in addressing this challenge is to distinguish protein surface loops that are likely to undergo backbone conformational changes upon protein-protein binding (mobile loops) from those that are not (stationary loops). In this study, we developed a machine learning strategy based on support vector machines (SVMs). Our SVM uses three features of loop residues in the unbound protein structures-Ramachandran angles, crystallographic beta-factors, and relative accessible surface area-to distinguish mobile loops from stationary ones. This method yields an average prediction accuracy of 75.3% compared with a random prediction accuracy of 50%, and an average of 0.79 area under the receiver operating characteristic (ROC) curve using cross-validation. Testing the method on an independent dataset, we obtained a prediction accuracy of 70.5%. Finally, we applied the method to 11 complexes that involve members from the Ras superfamily and achieved prediction accuracy of 92.8% for the Ras superfamily proteins and 74.4% for their binding partners.

• 出版日期2011-8