Capri/MR: exploring protein databases from a structural and physicochemical point of view

With the advent of high throughput systems to experimentally determine the three-dimensional (3-D) structure of proteins, molecular biologists are in urgent need of systems to automatically store, maintain and explore the vast structural databases that are thus being created. We have designed and implemented the Capri/MR system which makes it possible to identify families of protein structures, as contained in such very large 3-D protein structure databases. Our system is able to automatically index and search a database of proteins by three-dimensional shape, structural and/or physicochemical properties. For each of these diverse protein structure representations, we create a compact rotation and translation invariant index (or signature) which is placed in a database for future querying. A similarity search algorithm performs an exhaustive search against the entire database. Our search algorithm takes advantage of the compact signatures to rapidly find protein structures that are similar in 3-D shape and/or two-dimensional (2-D) properties. As a result, queries in our Capri/MR system run within a fraction of a second, and we are able to accurately group protein structures into the correct families, with very high precision and recall. In addition, our system dynamically processes new protein structures as they become available. We demonstrate the power of Capri/MR against the Protein Data Bank, which contains all known, experimentally determined, 3-D protein structures (48.000 as of January 2008). The main applications of our Capri/MR system lie in structural proteomics, protein evolution and mutation, as well as in drug design, in particular for studying the docking problem and the computer aided design of non-toxic drugs.