Surface-histogram: a new shape descriptor for protein-protein docking.

Determining the structure of protein-protein complexes remains a difficult and lengthy process, either by NMR or by X-ray crystallography. Several computational methods based on docking have been developed to support and even serve as possible alternatives to these experimental methods. In this article, we introduce a new protein-protein docking algorithm, shDock, based on shape complementarity. We characterize the local geometry on each protein surface with a new shape descriptor, the surface-histogram. We measure the complementarity between two surface-histograms, one on each protein, using a modified Manhattan distance. When a match is found between two local protein surfaces, a model is generated for the protein complex, which is then scored by checking for collision between the two proteins. We have tested our algorithm on Version 3 of the ZDOCK protein-protein docking benchmark. We found that for 110 out of the 124 test cases of bound docking in the benchmark, our algorithm was able to generate a model in the top 3600 candidates for the protein complex within an root-mean-square deviation of 2.5 Å from its native structure. For unbound docking predictions, we found a model within 2.5 Å in the top 3600 models in 54 out of 124 test cases. A comparison with other shape-based docking algorithms demonstrates that our approach gives significantly improved performance for both bound and unbound docking test cases.

Sampling the conformation of protein surface residues for flexible protein docking.

BACKGROUND: The problem of determining the physical conformation of a protein dimer, given the structures of the two interacting proteins in their unbound state, is a difficult one. The location of the docking interface is determined largely by geometric complementarity, but finding complementary geometry is complicated by the flexibility of the backbone and side-chains of both proteins. We seek to generate candidates for docking that approximate the bound state well, even in cases where there is backbone and/or side-chain difference from unbound to bound states. RESULTS: We divide the surfaces of each protein into local patches and describe the effect of side-chain flexibility on each patch by sampling the space of conformations of its side-chains. Likely positions of individual side-chains are given by a rotamer library; this library is used to derive a sample of possible mutual conformations within the patch. We enforce broad coverage of torsion space. We control the size of the sample by using energy criteria to eliminate unlikely configurations, and by clustering similar configurations, resulting in 50 candidates for a patch, a manageable number for docking. CONCLUSIONS: Using a database of protein dimers for which the bound and unbound structures of the monomers are known, we show that from the unbound patch we are able to generate candidates for docking that approximate the bound structure. In patches where backbone change is small (within 1 Å RMSD of bound), we are able to account for flexibility and generate candidates that are good approximations of the bound state (82% are within 1 Å and 98% are within 1.4 Å RMSD of the bound conformation). We also find that even in cases of moderate backbone flexibility our candidates are able to capture some of the overall shape change. Overall, in 650 of 700 test patches we produce a candidate that is either within 1 Å RMSD of the bound conformation or is closer to the bound state than the unbound is.

TreeQ-VISTA: an interactive tree visualization tool with functional annotation query capabilities.

UNLABELLED: We describe a general multiplatform exploratory tool called TreeQ-Vista, designed for presenting functional annotations in a phylogenetic context. Traits, such as phenotypic and genomic properties, are interactively queried from a user-provided relational database with a user-friendly interface which provides a set of tools for users with or without SQL knowledge. The query results are projected onto a phylogenetic tree and can be displayed in multiple color groups. A rich set of browsing, grouping and query tools are provided to facilitate trait exploration, comparison and analysis. AVAILABILITY: The program, detailed tutorial and examples are available online (http:/genome.lbl.gov/vista/TreeQVista).