ConTemplate Suggests Possible Alternative Conformations for a Query Protein of Known Structure

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. [Display omitted] •Most PDB proteins have multiple structures, often in various conformations•Two proteins that share one conformation often share additional conformations•ConTemplate suggests conformations for a query protein of known structure To conduct their function, proteins typically alternate between various conformations, but often only some of these important conformations are known. Narunsky et al. introduce the ConTemplate methodology and web server for inferring missing conformations of a query protein based on the structural repertoire in the PDB.