Recent Progress in Measuring Structural Similarity Between Proteins

Abstract

Surprisingly, after at least two decades of researches focused on the analysis of the similarity between protein three-dimensional structures, several new comparison methods were proposed during the last few years. These are briefly summarized and commented below. Some of the newly developed techniques are fast and were designed to handle large amounts of data and vast structural databases. Other methods are much slower and were developed to gain biological information by comparing distantly related protein structures. Additional studies were devoted to the problem of the multiple structural alignments and to strategies of comparison between alternative structural alignments.

Evolutionary inaccuracy of pairwise structural alignments

“…Methods vary in the details of their objective function, problem representation, null model of comparison statistics and approaches to searching alignment space (Alesker et al , 1996; Birzele et al , 2007; Chen and Crippen, 2005; Holm and Sander, 1993; Kifer et al , 2011; Kolodny et al , 2005; Lackner et al , 2000; Novosad et al , 2010; Pandit and Skolnick, 2008; Shibberu and Holder, 2011; Shindyalov and Bourne, 1998; Taylor, 1999; Vesterstrom and Taylor, 2006; Zhang and Skolnick, 2004), Reviewed in Carugo (2007). Common variations include the use of flexible alignment (Mosca et al , 2008; Rocha et al , 2009; Salem et al , 2010; Shatsky et al , 2004; Ye and Godzik, 2003) or using fragments and topological filters for initial alignments to improve quality and speed (Budowski-Tal et al , 2010; Gibrat et al , 1996; Krissinel and Henrick, 2004; Veeramalai et al , 2009).…”

Clustering tendency in the protein fold space

“…A very wide variety of techniques were used to compare pairs of protein structures[9–11]. In the present manuscript, we used a technique that allows one to represent a structure with a geometrical point in a n-dimensional space and to select a random (geometrical) point in the fold space (this is necessary to evaluate to clustering tendency; see below).…”

▪ Introduction

“…Even though proteins are all composed of only 20 amino acids, each protein has a 3 dimensional native structure (physiologically folded) that is specified by its primary structure, so that it has a unique set of characteristics (Voet and Voet 2004). The 3D structure of a protein and its ability to carry out its correct biological function are very tightly linked such that small structural defects can lead to a number of protein folding diseases (Carugo 2007). …”