Faculty Publications

Title

Detecting non-trivial protein structure relationships

Document Type

Article

Keywords

Alignment algorithms, Protein structure, Structural alignment, Structure comparison

Journal/Book/Conference Title

Current Bioinformatics

Volume

11

Issue

2

First Page

234

Last Page

242

Abstract

Automated methods for protein three-dimensional structure comparison play an important role in understanding protein function, evolution and biochemical reaction mechanisms. Since the tertiary structure of proteins is more conserved than their amino-acid sequences, accurately aligning three-dimensional structures allows to detect homology between proteins in the “twilight zone”, those sharing less than ~25% sequence identity. Unfortunately, existing methods for protein structure comparison are often unable to properly compare and align proteins related by complex structural modifications, such as circular permutations, large conformational changes and large residue insertions and deletions. In this paper, we present an algorithm capable of computing biologically meaningful alignments from structurally homologous but spatially distant fragments. Accurate alignments of proteins that have undergone large conformational variations are derived from multiple spatial superpositions. For mild to moderate conformational variations, approximate rigid body superpositions are recursively relaxed to allow matching of spatially distant regions. The algorithm incorporates an exact procedure for computing alignments of proteins related by circular permutations. We used two benchmarking datasets to demonstrate that our algorithm compares favorably to some of the most accurate methods available today. In the most difficult RIPC test set, the median accuracy of our method is 100%. The algorithm is freely available as a Web service at http://bioinfo.cs.uni.edu.

Original Publication Date

4-1-2016

DOI of published version

10.2174/1574893610666150624171116

Repository

UNI ScholarWorks, Rod Library, University of Northern Iowa

Language

en

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