Protein Structure and Function: Application of Bioinformatics Methods - John Rigden 2014

Fold Recognition
Introduction

Lawrence A. Kelley

Structure/29.html">Fold Recognition is closely linked to Cell/13.html">Protein Structure Prediction from Amino Acid Sequence, relying primarily on the identification of very distant homologs or analogs with known structures. Thus, this approach occupies a middle ground between ab initio protein folding Methods and modeling based on close Homology. This chapter provides a Historical Overview of the field, along with insights into recent breakthroughs—ranging from protein threading and sequence profile comparison to state-of-the-art meta-server Consensus Approaches and homology network analysis.

A protein's amino acid sequence dictates its three-dimensional structure, which, in turn, determines its biological function and MECHANISM OF ACTION. Protein folding serves as the vital link between the blueprint of living matter and living matter itself. Reflecting this core paradigm of biochemistry, nearly one in four Nobel Prizes in Chemistry since 1956 has been awarded for related research (Seringhaus and Gerstein 2007). In 2005, the journal Science named the protein folding problem one of the 125 biggest unsolved questions in science (Science Editorial 2005).

By the time this chapter was written¹, over 5.8 million unique protein sequences had been uncovered across hundreds of sequenced genomes. This number has grown exponentially over the past two decades and is likely to accelerate even further. Through emerging metagenomic initiatives—such as the Global Ocean Sampling expedition, which sequences random shotgun samples every 200 miles—as many as 1.3 million genes and 50,000 new species of organisms are discovered in a single barrel of seawater. Today, single-molecule sequencing instruments can sequence 100 million Base Pairs within 24 hours, a throughput expected to surge while sequencing costs continue to decline.

Lawrence A. Kelley

Structural Bioinformatics Group, Department of Biological Sciences,

Imperial College London, SW7 2AY, UK

e-mail: l.a.kelley@ic.ac.uk2009. Translator's Note.

Meanwhile, despite significant advancements in high-throughput structural Genomics and the round-the-clock operation of robotic NMR and X-ray crystallography pipelines dedicated to protein structure determination, only about 50,000 protein structures have been experimentally resolved to date².