Fingerprinting protein structures effectively and efficiently

Motivation: One common task in structural biology is to assess the similarities and differences among protein structures. A variety of structure alignment algorithms and programs has been designed and implemented for this purpose. A major drawback with existing structure alignment programs is that they require a large amount of computational time, rendering them infeasible for pairwise alignments on large collections of structures. To overcome this drawback, a fragment alphabet learned from known structures has been introduced. The method, however, considers local similarity only, and therefore occasionally assigns high scores to structures that are similar only in local fragments. Method: We propose a novel approach that eliminates false positives, through the comparison of both local and remote similarity, with little compromise in speed. Two kinds of contact libraries (ContactLib) are introduced to fingerprint protein structures effectively and efficiently. Each contact group of the contact library consists of one local or two remote fragments and is represented by a concise vector. These vectors are then indexed and used to calculate a new combined hit-rate score to identify similar protein structures effectively and efficiently. Results: We tested our method on the high-quality protein structure subset of SCOP30 containing 3297 protein structures. For each protein structure of the subset, we retrieved its neighbor protein structures from the rest of the subset. The best area under the ReceiverOperating Characteristic curve, archived by ContactLib, is as high as 0.960. This is a significant improvement compared with 0.747, the best result achieved by FragBag. We also demonstrated that incorporating remote contact information is critical to consistently retrieve accurate neighbor protein structures for all-� query protein structures. Availability and implementation: https://cs.uwaterloo.ca/*xfcui/ contactlib/.