An overview of comparative modelling and resources dedicated to large-scale modelling of genome sequences

Abstract

Computational modelling of proteins has been a major catalyst in structural biology. Bioinformatics groups have exploited the repositories of known structures to predict high-quality structural models with high efficiency at low cost. This article provides an overview of comparative modelling, reviews recent developments and describes resources dedicated to large-scale comparative modelling of genome sequences. The value of subclustering protein domain superfamilies to guide the template-selection process is investigated. Some recent cases in which structural modelling has aided experimental work to determine very large macromolecular complexes are also cited.

Keywords: comparative modelling; protein structure prediction; template selection; template-based modelling.

Figure 1

Structural conservation of structural domains classified in CATH FunFams and superfamilies.

Figure 2

Comparison of the quality of the top-ranked models produced by modelling protocols using functional families (FunFams) and a BLAST-based strategy. The models were assessed by perfoming a structural comparison with the known protein complexes. We used the assessment criteria adopted by the Critical Assessment of Prediction of Interactions (CAPRI) to classify the models into different categories based on the interface r.m.s.d. (i.r.m.s.d.) and fraction of native residue–residue contacts (Fnat) (Méndez et al., 2003 ▸).