Protein function involves conformational changes, but often, for a given protein, only some of these conformations are known. The missing conformations could be predicted using the wealth of data in the PDB. Most PDB proteins have multiple structures, and proteins sharing one similar conformation often share others as well. The ConTemplate web server (http://bental.tau.ac.il/contemplate) exploits these observations to suggest conformations for a query protein with at least one known conformation (or model thereof). We demonstrate ConTemplate on a ribose-binding protein that undergoes significant conformational changes upon substrate binding. Querying ConTemplate with the ligand-free (or bound) structure of the protein produces the ligand-bound (or free) conformation with a root-mean-square deviation of 1.7 Å (or 2.2 Å); the models are derived from conformations of other sugar-binding proteins, sharing approximately 30% sequence identity with the query. The calculation also suggests intermediate conformations and a pathway between the bound and free conformations.
Bibliographical noteFunding Information:
We thank Ron Diskin, Sarel Fleishman, Amit Kessel, and Meytal Landau for helpful discussions, and Vladimir Kadaner for technical support. This work was supported by grant No. 1775/12 of the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation. A.N. and H.A. were funded in part by the Edmond J. Safra Center for Bioinformatics at Tel Aviv University.
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ASJC Scopus subject areas
- Structural Biology
- Molecular Biology