The proteome: structure, function and evolution

Abstract

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk. Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein (http://www.e-protein.org/). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

Quantitative sequence-function relationships in proteins based on gene ontology

“…Fleming et al . [ 17 ] combined structural and sequence alignments of proteins in an annotation tool named PHUNCTIONER.…”

Salivary and pellicle proteome: A datamining analysis

“…Linking different datasets with each other and applying a range of bioinformatic analysis tools allows to generate a reliable and valid database, and to move from pure molecular description of single proteins to systems biology and the identification of key proteins for possible medical applications2122. For example, data from different repositories and sources were combined to define the core proteins of the human proteome, with GO annotation being used to identify signaling sequences for protein (re)localization and molecular organization152324.…”

Are predicted protein structures of any value for binding site prediction and virtual ligand screening?

“…Some approaches locate binding sites by a geometric match to three-dimensional descriptors or templates of biologically relevant sites [5,6]. More powerful is the evolutionary trace methodology that combines protein structure with conserved residue patterns mapped onto the protein’s surface [7–9].…”