Integrating Computational Protein Function Prediction into Drug Discovery Initiatives

Pharmaceutical researchers must evaluate vast numbers of protein sequences and formulate innovative strategies to identify valid targets and discover leads against them in order to accelerate drug discovery. The ever-increasing number and diversity of novel protein sequences identified by genomic sequencing projects and the success of worldwide structural genomics initiatives have spurred great interest and impetus in the development of methods for accurate, computationally empowered protein function prediction and active site identification. Previously, in the absence of direct experimental evidence, homology-based protein function annotation remained the gold standard for in silico analysis and prediction of protein function. However, with the continued exponential expansion of sequence databases, this approach is not always applicable, as fewer query protein sequences demonstrate significant homology to protein gene products of known function. As a result, several non-homology-based methods for protein function prediction that are based on sequence features, structure, evolution, biochemical, and genetic knowledge have emerged. This works reviews current bioinformatic programs and approaches for protein function prediction/annotation and discusses their integration into drug discovery initiatives. The development of such methods to annotate protein functional sites and their application to large protein functional families is crucial to successfully using the vast amounts of genomic sequence information available to drug discovery and development processes. Drug Dev Res 72: 4-16, 2011. (C) 2010 Wiley-Liss, Inc.