Fast Multiple Alignment of Protein Structures Using Conformational Letter Blocks

Most approaches for protein structure alignment start from a search for similar fragments since this local similarity is necessary to the alignment even though is insufficient. In contrary to the sequence alignment, any insignificant trial alignment for structures can be detected by structure superposition and then excluded. It is then practicable to select from locally similar fragments those responsible for alignment and build up it. An efficient way for local similarity search is to use a conformational alphabet, which is a discretized description of protein chain local geometry. Using our conformational alphabet and its substitution matrix CLESUM, we propose a tool called BLOMAPS for fast multiple structure alignment. By means of the conformational alphabet, a structural fragment is mapped to a string, and two strings with their CLESUM score being higher than a preset threshold form a similar fragment pair (SFP). A string from one protein as a seed and its highly similar fragments from other proteins form a similar fragment block. Taking one protein as the pivot, BLOMAPS uses the rigid transformation for SFPs in a block to superimpose proteins and initiate an anchor-based alignment. BLOMAPS is greedy in nature, guided by CLESUM similarity scores. It consists of several steps including finding similar fragment blocks based on a pivot protein, removing block redundancy, constructing scaffold by checking consistency in spatial arrangement among fragments from different blocks, dealing with unanchored structures, and the final step of refinement where the average template for alignment is obtained and motifs missing from the pivot protein are found and added. The utility of BLOMAPS is tested on various protein structure ensembles including large scale ones, and compared with several other tools including MATT. BLOMAPS is available at: www.itp.ac.cn/zheng/blomaps.rar