A new generation of statistical potentials for proteins.
We propose a novel and flexible derivation scheme of statistical, database-derived, potentials, which allows one to take simultaneously into account specific correlations between several sequence and structure descriptors. This scheme leads to the decomposition of the total folding free energy of a protein into a sum of lower order terms, thereby giving the possibility to analyze independently each contribution and clarify its significance and importance, to avoid overcounting certain contributions, and to deal more efficiently with the limited size of the database. In addition, this derivation scheme appears as quite general, for many previously developed potentials can be expressed as particular cases of our formalism. We use this formalism as a framework to generate different residue-based energy functions, whose performances are assessed on the basis of their ability to discriminate genuine proteins from decoy models. The optimal potential is generated as a combination of several coupling terms, measuring correlations between residue types, backbone torsion angles, solvent accessibilities, relative positions along the sequence, and interresidue distances. This potential outperforms all tested residue-based potentials, and even several atom-based potentials. Its incorporation in algorithms aiming at predicting protein structure and stability should therefore substantially improve their performances.
Unité de Bioinformatique génomique et structurale, Université Libre de Bruxelles, 1050 Brussels, Belgium. ydehouck@ulb.ac.be
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Dehouck
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Gilis
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Rooman
D000465:Algorithms; D019295:Computational Biology; D030562:Databases, Protein; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013223:Statistics as Topic; D013816:Thermodynamics
D011506:Proteins