Mining the entire Protein DataBank for frequent spatially cohesive amino acid patterns.

Pieter Meysman,Cheng Zhou,Bart Goethals,Kris Laukens,Boris Cule

doi:10.1186/s13040-015-0038-4

Abstract

BackgroundThe three-dimensional structure of a protein is an essential aspect of its functionality. Despite the large diversity in protein structures and functionality, it is known that there are common patterns and preferences in the contacts between amino acid residues, or between residues and other biomolecules, such as DNA. The discovery and characterization of these patterns is an important research topic within structural biology as it can give fundamental insight into protein structures and can aid in the prediction of unknown structures.ResultsHere we apply an efficient spatial pattern miner to search for sets of amino acids that occur frequently in close spatial proximity in the protein structures of the Protein DataBank. This allowed us to mine for a new class of amino acid patterns, that we term FreSCOs (Frequent Spatially Cohesive Component sets), which feature synergetic combinations. To demonstrate the relevance of these FreSCOs, they were compared in relation to the thermostability of the protein structure and the interaction preferences of DNA-protein complexes. In both cases, the results matched well with prior investigations using more complex methods on smaller data sets.ConclusionsThe currently characterized protein structures feature a diverse set of frequent amino acid patterns that can be related to the stability of the protein molecular structure and that are independent from protein function or specific conserved domains.Electronic supplementary materialThe online version of this article (doi:10.1186/s13040-015-0038-4) contains supplementary material, which is available to authorized users.

Highlights

The three-dimensional structure of a protein is an essential aspect of its functionality
Triplet patterns feature synergetic combinations The entire non-redundant Protein DataBank (PDB) data set can be mined for Frequent spatially cohesive component set (FreSCO), i.e. patterns of amino acids that frequently occur in close proximity
It may be that the chemical interaction is only present between two of the amino acids, such as the FreSCOs featuring a basic and an acidic amino acid, and the third amino acid provides the necessary context for this interaction, for example a hydrophilic or hydrophobic residue

Summary

Introduction

The three-dimensional structure of a protein is an essential aspect of its functionality. Despite the large diversity in protein structures and functionality, it is known that there are common patterns and preferences in the contacts between amino acid residues, or between residues and other biomolecules, such as DNA. Proteins are primarily composed of a long chain of amino acids that is folded into a complex three-dimensional structure. This spatial structure of a protein is an essential component in its functionality and is subjected to evolutionary pressures to optimize the inter-residue contacts that support it. Despite the large diversity in protein structures and functionality, it is known that there are common patterns and contact preferences between residues, or even between residues and other biomolecules, such as DNA.

Methods

Results

Conclusion