Using ConTemplate and the PDB to explore conformational space: on the detection of rare protein conformations

Conformational changes mediate important protein functions, such as opening and closing of channel gates, activation and inactivation of enzymes, etc. The entire conformational repertoire of a given query protein may not be known; however, it may be possible to infer unknown conformations from other proteins. We developed the ConTemplate method to exploit the richness of the Protein Data Bank (PDB)[1] for this purpose. ConTemplate uses a three-step process to suggest alternative conformations for a query protein with one known conformation [2]. First, ConTemplate uses GESAMT to scan the PDB for proteins that share structural similarity with the query [3]. Next, for each of the collected proteins, additional known conformations are detected using BLAST [4], and clustered into a predefined number of clusters [5]. Finally, MODELLER [6] builds models of the query in various conformations, each representative of a cluster.