TOPS++FATCAT: Fast flexible structural alignment using constraints derived from TOPS+ Strings Model

We developed a TOPS++FATCAT algorithm that uses an intuitive description of the proteins' structures as captured in the popular TOPS diagrams to limit the search space of the aligned fragment pairs (AFPs) in the flexible alignment of protein structures performed by the FATCAT algorithm. The TOPS++FATCAT algorithm is faster than FATCAT by more than an order of magnitude with a minimal cost in classification and alignment accuracy. For beta-rich proteins its accuracy is better than FATCAT, because the TOPS+ strings models contains important information of the parallel and anti-parallel hydrogen-bond patterns between the beta-strand SSEs (Secondary Structural Elements). We show that the TOPS++FATCAT errors, rare as they are, can be clearly linked to oversimplifications of the TOPS diagrams and can be corrected by the development of more precise secondary structure element definitions.The benchmark analysis results and the compressed archive of the TOPS++FATCAT program for Linux platform can be downloaded from the following web site: http://fatcat.burnham.org/TOPS/ webciteTOPS++FATCAT provides FATCAT accuracy and insights into protein structural changes at a speed comparable to sequence alignments, opening up a possibility of interactive protein structure similarity searches.Structural biology is one of the most successful fields of modern biology. Over 50,000 solved protein structures illustrate details of many specific biological processes. The same data also provide us with information about the global features of protein structure space and can be studied to discover the evolutionary, physical, and mathematical rules governing them. How many fundamentally different protein shapes (folds) are there? How do protein structures evolve? How do new structural features appear, and if they are coupled with changes in function, how does this process occur? Such questions can be studied by classifying, comparing and analyzing known protein structures. Two different, but syner