Large-Scale Prediction of Protein Structure and Function from Sequence

Abstract

The identification of novel drug targets from genomic data involves the large-scale analysis of many protein sequences. Methods for automated structure and function prediction are an essential tool for this purpose. In this review we concentrate on the recent developments in the field of protein structure prediction and how these can be used to gain hints about the function of proteins. The current state-of-the-art is highlighted through recent community-wide experiments aimed at comparing different approaches. For structure prediction this allows the identification of key improvements to increase the crucial sequence to structure alignment needed for accurate models. Function prediction is a rapidly maturing field that is still being benchmarked. Definitions for protein function are presented and available methods, mostly concentrating on functional site descriptors and structural motifs, presented.

Rapid Annotation of Anonymous Sequences from Genome Projects Using Semantic Similarities and a Weighting Scheme in Gene Ontology

“…789 genomes have been completed and over 1,600 are in progress assembly (as of November 2008). This means that thousands of raw sequences are readily obtainable, but the challenge now [1] is to assign them a putative function and to keep the annotation up-to-date [2]. The results are difficult to interpret, especially when the retrieved hits share low sequence identity with the starting query or when restricted local alignments identify a single domain in multi-domain protein hits or, finally, when the updating state of protein hits is incomplete and even contradictory making functional transfer difficult [3].…”

Proteomics and Cardiovascular Disease: An Update

“…Proteomics is the large-scale study of expression, function, and interaction of the complement of proteins in an organism (in health and disease) or cell type at a given time [5]. Alterations or modifications that occur at transcriptional, translational and posttranslational levels contribute to the regulation of protein activity and further enhance proteomic complexity [5][6][7] (Fig. 1).…”

Improving the quality of protein structure models by selecting from alignment alternatives

“…Recently, a lot of effort has gone into the development of Model Quality Assessment Programs (MQAPs) [ 12 - 14 ]. MQAPs are computer programs that receive as input a 3D model of a protein structure and produce as output a real number representing the quality of the model [ 15 ].…”