Similarity Search for Local Protein Structures at Atomic Resolution by Exploiting a Database Management System

Overview

Journal Biophysics (Nagoya-shi)

Specialty Biophysics

Date 2016 Nov 19

PMID 27857569

Citations 13

Authors

Akira R Kinjo

Haruki Nakamura

Affiliations

Soon will be listed here.

Abstract

A method to search for local structural similarities in proteins at atomic resolution is presented. It is demonstrated that a huge amount of structural data can be handled within a reasonable CPU time by using a conventional relational database management system with appropriate indexing of geometric data. This method, which we call geometric indexing, can enumerate ligand binding sites that are structurally similar to sub-structures of a query protein among more than 160,000 possible candidates within a few hours of CPU time on an ordinary desktop computer. After detecting a set of high scoring ligand binding sites by the geometric indexing search, structural alignments at atomic resolution are constructed by iteratively applying the Hungarian algorithm, and the statistical significance of the final score is estimated from an empirical model based on a gamma distribution. Applications of this method to several protein structures clearly shows that significant similarities can be detected between local structures of non-homologous as well as homologous proteins.

Citing Articles

Protein Data Bank Japan (PDBj): updated user interfaces, resource description framework, analysis tools for large structures.

Kinjo A, Bekker G, Suzuki H, Tsuchiya Y, Kawabata T, Ikegawa Y Nucleic Acids Res. 2016; 45(D1):D282-D288.

PMID: 27789697 PMC: 5210648. DOI: 10.1093/nar/gkw962.

GIRAF: a method for fast search and flexible alignment of ligand binding interfaces in proteins at atomic resolution.

Kinjo A, Nakamura H Biophysics (Nagoya-shi). 2016; 8:79-94.

PMID: 27493524 PMC: 4629647. DOI: 10.2142/biophysics.8.79.

Landscape of protein-small ligand binding modes.

Kasahara K, Kinoshita K Protein Sci. 2016; 25(9):1659-71.

PMID: 27327045 PMC: 5338237. DOI: 10.1002/pro.2971.

Considerations of Protein Subpockets in Fragment-Based Drug Design.

Bartolowits M, Davisson V Chem Biol Drug Des. 2015; 87(1):5-20.

PMID: 26307335 PMC: 5464946. DOI: 10.1111/cbdd.12631.

Mg2+-dependent interactions of ATP with the cystathionine-β-synthase (CBS) domains of a magnesium transporter.

Hirata Y, Funato Y, Takano Y, Miki H J Biol Chem. 2014; 289(21):14731-9.

PMID: 24706765 PMC: 4031528. DOI: 10.1074/jbc.M114.551176.

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