sas-pro simultaneous residue assignment and structure superposition for protein structure alignmentsas-pro同时剩余分配和结构对蛋白质结构对齐叠加.pdfVIP

SAS-Pro: Simultaneous Residue Assignment and Structure Superposition for Protein Structure Alignment 1 1,2 Shweta B. Shah , Nikolaos V. Sahinidis * 1 Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America, 2 Lane Center for Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America Abstract Protein structure alignment is the problem of determining an assignment between the amino-acid residues of two given proteins in a way that maximizes a measure of similarity between the two superimposed protein structures. By identifying geometric similarities, structure alignment algorithms provide critical insights into protein functional similarities. Existing structure alignment tools adopt a two-stage approach to structure alignment by decoupling and iterating between the assignment evaluation and structure superposition problems. We introduce a novel approach, SAS-Pro, which addresses the assignment evaluation and structure superposition simultaneously by formulating the alignment problem as a single bilevel optimization problem. The new formulation does not require the sequentiality constraints, thus generalizing the scope of the alignment methodology to include non-sequential protein alignments. We employ derivative-free optimization methodologies for searching for the global optimum of the highly nonlinear and non-differentiable RMSD function encountered in the proposed model. Alignments obtained with SAS-Pro have better RMSD values and larger lengths than those obtained from other alignment tools. For non-sequential alignment problems, SAS-Pro leads to alignments with high degree of sim