Structural bioinformatics

نویسندگان

  • J. Bernauer
  • J. Azé
  • J. Janin
  • A. Poupon
  • Anna Tramontano
چکیده

Motivation: Protein-protein complexes are known to play key roles in many cellular processes. However, they are often not accessible to experimental study because of their low stability and difficulty to produce the proteins and assemble them in native conformation. Thus, docking algorithms have been developed to provide an in silico approach of the problem. A protein-protein docking procedure traditionally consists in two successive tasks: a search algorithm generates a large number of candidate solutions, and then a scoring function is used to rank them. Results: To address the second step, we developed a scoring function based on a Voronoï tessellation of the protein threedimensional structure. We showed that the Voronoï representation may be used to describe in a simplified but useful manner, the geometric and physico-chemical complementarities of two molecular surfaces. We measured a set of parameters on native proteinprotein complexes and on decoys, and used them as attributes in several statistical learning procedures: a logistic function, Support Vector Machines (SVM), and a genetic algorithm. For the later, we used ROGER, a genetic algorithm designed to optimize the area under the ROC curve. To further test the scores derived with ROGER, we ranked models generated by two different docking algorithms on targets of a blind prediction experiment, improving in almost all cases the rank of native-like solutions. Availability: http://genomics.eu.org/spip/-Bioinformatics-tools-

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تاریخ انتشار 2007