CRD: A de novo design algorithm for the prediction of cognate protein receptors for small molecule ligands.

While predicting a ligand that binds to a protein is feasible with current methods, the opposite, i.e., the prediction of a receptor for a ligand remains challenging.

Structural similarities between SAM and ATP recognition motifs and detection of ATP binding in a SAM binding DNA methyltransferase.

S-adenosylmethionine (SAM) is a ubiquitous co-factor that serves as a donor for methylation reactions and additionally serves as a donor of other functional groups such as amino and ribosyl moieties in a variety of other biochemical reactions. Such versatility in function is enabled by the ability of SAM to be recognized by a wide variety of protein molecules that vary in their sequences and structural folds. To understand what gives rise to specific SAM binding in diverse proteins, we set out to study if there are any structural patterns at their binding sites.

Fast Local Alignment of Protein Pockets (FLAPP): A System-Compiled Program for Large-Scale Binding Site Alignment.

Protein function is a direct consequence of its sequence, structure, and the arrangement at the binding site. Bioinformatics using sequence analysis is typically used to gain a first insight into protein function. Protein structures, on the other hand, provide a higher resolution platform into understanding functions.

SiteMotif: A graph-based algorithm for deriving structural motifs in Protein Ligand binding sites.

Studying similarities in protein molecules has become a fundamental activity in much of biology and biomedical research, for which methods such as multiple sequence alignments are widely used. Most methods available for such comparisons cater to studying proteins which have clearly recognizable evolutionary relationships but not to proteins that recognize the same or similar ligands but do not share similarities in their sequence or structural folds. In many cases, proteins in the latter class share structural similarities only in their binding sites.

A Multi-Pronged Computational Pipeline for Prioritizing Drug Target Strategies for Latent Tuberculosis.

Tuberculosis is one of the deadliest infectious diseases worldwide and the prevalence of latent tuberculosis acts as a huge roadblock in the global effort to eradicate tuberculosis. Most of the currently available anti-tubercular drugs act against the actively replicating form of (), and are not effective against the non-replicating dormant form present in latent tuberculosis. With about 30% of the global population harboring latent tuberculosis and the requirement for prolonged treatment duration with the available drugs in such cases, the rate of adherence and successful completion of therapy is low.

Metabolic origin of the fused aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase.

About 1 billion years ago, in a single-celled holozoan ancestor of all animals, a gene fusion of two tRNA synthetases formed the bifunctional enzyme, glutamyl-prolyl-tRNA synthetase (EPRS). We propose here that a confluence of metabolic, biochemical, and environmental factors contributed to the specific fusion of glutamyl- (ERS) and prolyl- (PRS) tRNA synthetases. To test this idea, we developed a mathematical model that centers on the precursor-product relationship of glutamic acid and proline, as well as metabolic constraints on free glutamic acid availability near the time of the fusion event.

An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships.