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Computational study for protein-protein docking using global optimization and empirical potentials.

ABSTRACT: Protein-protein interactions are important for biochemical processes in biological systems. The 3D structure of the macromolecular complex resulting from the protein-protein association is a very useful source to understand its specific functions. This work focuses on computational study for protein-protein docking, where the individually crystallized structures of interacting proteins are treated as rigid, and the conformational space generated by the two interacting proteins is explored extensively. The energy function consists of intermolecular electrostatic potential, desolvation free energy represented by empirical contact potential, and simple repulsive energy terms. The conformational space is six dimensional, represented by translational vectors and rotational angles formed between two interacting proteins. The conformational sampling is carried out by the search algorithms such as simulated annealing (SA), conformational space annealing (CSA), and CSA combined with SA simulations (combined CSA/SA). Benchmark tests are performed on a set of 18 protein-protein complexes selected from various protein families to examine feasibility of these search methods coupled with the energy function above for protein docking study.

SUBMITTER: Lee K

PROVIDER: S-EPMC2635596 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Computational study for protein-protein docking using global optimization and empirical potentials.

Lee Kyoungrim K

International journal of molecular sciences 20080122 1

Protein-protein interactions are important for biochemical processes in biological systems. The 3D structure of the macromolecular complex resulting from the protein-protein association is a very useful source to understand its specific functions. This work focuses on computational study for protein-protein docking, where the individually crystallized structures of interacting proteins are treated as rigid, and the conformational space generated by the two interacting proteins is explored extens ...[more]

PMID: 19325720

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Project description:BackgroundIn structural genomics, an important goal is the detection and classification of protein-protein interactions, given the structures of the interacting partners. We have developed empirical energy functions to identify native structures of protein-protein complexes among sets of decoy structures. To understand the role of amino acid diversity, we parameterized a series of functions, using a hierarchy of amino acid alphabets of increasing complexity, with 2, 3, 4, 6, and 20 amino acid groups. Compared to previous work, we used the simplest possible functional form, with residue-residue interactions and a stepwise distance-dependence. We used increased computational resources, however, constructing 290,000 decoys for 219 protein-protein complexes, with a realistic docking protocol where the protein partners are flexible and interact through a molecular mechanics energy function. The energy parameters were optimized to correctly assign as many native complexes as possible. To resolve the multiple minimum problem in parameter space, over 64000 starting parameter guesses were tried for each energy function. The optimized functions were tested by cross validation on subsets of our native and decoy structures, by blind tests on series of native and decoy structures available on the Web, and on models for 13 complexes submitted to the CAPRI structure prediction experiment.ResultsPerformance is similar to several other statistical potentials of the same complexity. For example, the CAPRI target structure is correctly ranked ahead of 90% of its decoys in 6 cases out of 13. The hierarchy of amino acid alphabets leads to a coherent hierarchy of energy functions, with qualitatively similar parameters for similar amino acid types at all levels. Most remarkably, the performance with six amino acid classes is equivalent to that of the most detailed, 20-class energy function.ConclusionThis suggests that six carefully chosen amino acid classes are sufficient to encode specificity in protein-protein interactions, and provide a starting point to develop more complicated energy functions.

Dataset Information

Computational study for protein-protein docking using global optimization and empirical potentials.

Publications

Computational study for protein-protein docking using global optimization and empirical potentials.

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