Prediction of Protein Sites and Physicochemical Properties Related to Functional Specificity.

Florencio Pazos

doi:10.3390/bioengineering8120201

Abstract

Specificity Determining Positions (SDPs) are protein sites responsible for functional specificity within a family of homologous proteins. These positions are extracted from a family’s multiple sequence alignment and complement the fully conserved positions as predictors of functional sites. SDP analysis is now routinely used for locating these specificity-related sites in families of proteins of biomedical or biotechnological interest with the aim of mutating them to switch specificities or design new ones. There are many different approaches for detecting these positions in multiple sequence alignments. Nevertheless, existing methods report the potential SDP positions but they do not provide any clue on the physicochemical basis behind the functional specificity, which has to be inferred a-posteriori by manually inspecting these positions in the alignment. In this work, a new methodology is presented that, concomitantly with the detection of the SDPs, automatically provides information on the amino-acid physicochemical properties more related to the change in specificity. This new method is applied to two different multiple sequence alignments of homologous of the well-studied RasH protein representing different cases of functional specificity and the results discussed in detail.

Highlights

Specificity Determining Positions (SDPs) are protein sites responsible for functional specificity within a family of homologous proteins
Existing methods report the potential SDP positions but they do not provide any clue on the physicochemical basis behind the functional specificity, which has to be inferred a-posteriori by manually inspecting these positions in the alignment
A new methodology is presented that, concomitantly with the detection of the SDPs, automatically provides information on the amino-acid physicochemical properties more related to the change in specificity. This new method is applied to two different multiple sequence alignments of homologous of the well-studied RasH protein representing different cases of functional specificity and the results discussed in detail

Summary

Introduction

Specificity Determining Positions (SDPs) are protein sites responsible for functional specificity within a family of homologous proteins. A new methodology is presented that, concomitantly with the detection of the SDPs, automatically provides information on the amino-acid physicochemical properties more related to the change in specificity This new method is applied to two different multiple sequence alignments of homologous of the well-studied RasH protein representing different cases of functional specificity and the results discussed in detail. Bioinformatics approaches have been developed to distill useful information from these large amounts of data [3], complementing the more expensive and time-consuming experimental approaches These in-silico approaches, which take advantage of this deluge of sequence information, allow, among other things, to predict a protein’s function and its functional/active sites, structural features including its three-dimensional structure, interactions with other proteins and small molecules, etc.

Methods

Results

Conclusion