A structural alphabet for local protein structures: Improved prediction methods

Abstract

Three-dimensional protein structures can be described with a library of 3D fragments that define a structural alphabet. We have previously proposed such an alphabet, composed of 16 patterns of five consecutive amino acids, called Protein Blocks (PBs). These PBs have been used to describe protein backbones and to predict local structures from protein sequences. The Q16 prediction rate reaches 40.7% with an optimization procedure. This article examines two aspects of PBs. First, we determine the effect of the enlargement of databanks on their definition. The results show that the geometrical features of the different PBs are preserved (local RMSD value equal to 0.41 A on average) and sequence-structure specificities reinforced when databanks are enlarged. Second, we improve the methods for optimizing PB predictions from sequences, revisiting the optimization procedure and exploring different local prediction strategies. Use of a statistical optimization procedure for the sequence-local structure relation improves prediction accuracy by 8% (Q16 = 48.7%). Better recognition of repetitive structures occurs without losing the prediction efficiency of the other local folds. Adding secondary structure prediction improved the accuracy of Q16 by only 1%. An entropy index (Neq), strongly related to the RMSD value of the difference between predicted PBs and true local structures, is proposed to estimate prediction quality. The Neq is linearly correlated with the Q16 prediction rate distributions, computed for a large set of proteins. An "expected" prediction rate QE16 is deduced with a mean error of 5%.

Protein contacts, inter-residue interactions and side-chain modelling

“…The absence of assignment for an important proportion of residues has led to the emergence of new approaches based on local protein structure libraries called structural alphabets able to approximate all local protein structures [8][9][10][11][12][13][14]. This kind of approach has proven its relevance by enabling local structure prediction [13,15], structural alignments [16][17][18] and the discovery of functional local structural motifs [19].…”

Species specific amino acid sequence–protein local structure relationships: An analysis in the light of a structural alphabet

“…-PBs prediction and influence of specie context. 100 independent simulations have been carried out to predict PBs using a Bayesian prediction procedure (de Brevern et al, 2000;Etchebest et al, 2005;Tyagi et al, 2009b). From left to right (x axis), each label (NR, Sc, At and Pf) indicates databank on which the training is carried out.…”

“…The three specialized databanks (Sc, At and Pf) represents 202,410, 173,450 and 36,175 amino acid residues respectively. With regards to our previous studies de Brevern, 2005;de Brevern et al, 2000;de Brevern et al, 2002;de Brevern et al, 2004;Etchebest et al, 2005;Fourrier et al, 2004), the number of amino acids in each databank is sufficient to analyze the sequence -structure relationships in terms of secondary structure and Protein Blocks (Tyagi et al, 2009b).…”

“…PB assignment has been made using an in-house tool (available at http://www.dsimb.inserm.fr/DOWN/LECT/), similar assignment is also made by PBE web server (http://bioinformatics.univ-reunion.fr/PBE/) (Tyagi et al, 2006). They have been used to describe the 3D protein backbones (de Brevern, 2005) and to perform local structure prediction (Benros et al, 2009;de Brevern et al, 2000;de Brevern et al, 2004;Dong et al, 2008;Etchebest et al, 2005;Rangwala et al, 2009;Zimmermann and Hansmann, 2008). PB based approaches have been proved to be effective in prediction based on protein sequence-structure relationships Li et al, 2009;Tyagi et al, 2009b).…”

“…The amino acid occurrences in each secondary structure and PB have been normalized into a Z-score: Protein Blocks in our earlier works (Benros et al, 2009;Benros et al, 2006;de Brevern and Hazout, 2001;de Brevern and Hazout, 2003;de Brevern et al, 2000;de Brevern et al, 2002;de Brevern et al, 2007;de Brevern et al, 2004;Etchebest et al, 2005;Etchebest et al, 2007;Ghozlane et al, 2009). …”