Current Pharmaceutical Biotechnology - Volume 9, Issue 2, 2008

The ultimate goal of pharmacology and biotechnology is to develop drugs that could prevent or cure human diseases. Despite of the enormous progress made in experimental techniques, still discovering a new drug is an expensive and lengthy procedure. Structure-based drug discovery techniques offer fast and efficient alternative to the experimental approaches. Since protein-protein interactions are essential for the fu Read More

The protein-protein docking problem is one of the focal points of activity in computational structural biology. Adequate computational techniques for structural modeling of protein interactions are important because of the growing number of known protein structures, particularly in the context of structural genomics. The protein docking methodology offers tools for fundamental studies of protein interactions and provides struct Read More

Complex protein-protein interaction networks govern biological processes in cells. Protein interfaces are the sites where proteins physically interact. Identification and characterization of protein interfaces will lead to understanding how proteins interact with each other and how they are involved in protein-protein interaction networks. What makes a given interface bind to different proteins; how similar/different the interactions in Read More

The ability to predict the three-dimensional structure of a protein complex starting from the isolated binding partners is becoming increasingly relevant. As our understanding of the molecular mechanisms behind protein-protein binding improves, so do the docking methods, however, it remains a challenge to adequately predict the unbound to bound transition. Side-chain flexibility is routinely handled and most docking Read More

The functional capabilities of biological systems, such as enzyme catalysis, nutrient import, and cell signaling, depend crucially on specific molecular interactions. In addition, the effects of common drugs also act through a mechanism of binding to specific biomolecular targets. Models for the prediction of binding affinity are used in basic research to study the molecular basis of biological function as well as in applied research t Read More

Ionic strength- (or salt-) effects on the protein-protein binding free energy has been included in many computational studies, while comparatively fewer computational studies have looked at the corresponding effect of pH. The pH dependence can be very complex if several groups change protonation state, while the ionic strength dependence usually scales as ln(I), and the main challenge is to predict the magnitude of the Read More

Protein-protein interactions (PPIs) have a pivotal role in many biological processes suggesting that targeting macromolecular complexes will open new avenues for the design of the next generation of therapeutics. A wide range of “in silico methods” can be used to facilitate the design of protein-protein modulators. Among these methods, virtual ligand screening, protein-protein docking, structural predictions and druggabl Read More

Almost all (99.9%) nucleotide bases are exactly the same in all people, however, the remaining 0.1% account for about 1.4 million locations where single-base DNA differences/polymorphisms (SNPs) occur in humans. Some of these SNPs, called non-synonymous SNPs (nsSNPs), result in a change of the amino acid sequences of the corresponding proteins affecting protein functions and interactions. This review summarizes Read More