Current Pharmaceutical Design - Volume 19, Issue 26, 2013

Multiple approaches have been devised and evaluated to computationally estimate binding free energies. Results using a recently developed Quantum Mechanics (QM)/Molecular Mechanics (MM) based Free Energy Perturbation (FEP) method suggest that this method has the potential to provide the most accurate estimation of binding affinities to date. The method treats ligands/inhibitors using QM while using MM for the r Read More

These are exciting times for bioinformaticians, computational biologists and drug designers with the genome and proteome sequences and related structural databases growing at an accelerated pace. The post-genomic era has triggered high expectations for a rapid and successful treatment of diseases. However, in this biological information rich and functional knowledge poor scenario, the challenges are indeed grand, no les Read More

This review highlights some recent advances in the design and development of matrix metalloproteinase inhibitors, especially those targeting MMP-2, MMP-9, and MMP-13. Various zinc-binding groups and non-zinc-binding groups are discussed. Interactions between residues in the critical S1' specificity pocket and MMP inhibitors are given special attention. The influence of ionization states of hydroxamates and retrohydroxam Read More

Kinases are one of the most popular classes of drug targets as they are involved in signal transduction pathways, which are wired through a phosphotransfer cascade and elicit a number of important and essential physiological responses. Kinase specificity has emerged as one of the major issues to be addressed in drug discovery approaches. In most kinases the active site is the ATP binding site and finding suitable hit Read More

This article reviews some of our experiences on applying computational techniques to aid the design of drugs targeting protein kinases and phosphatases. It is not a comprehensive review. Rather, it focuses on several less explored approaches or ideas that we have experiences on. It reviews some recent improvements on the Poisson-Boltzmann/Surface Area model for calculating binding affinity and discusses ways to Read More

Glycogen Synthase Kinase-3 (GSK-3) is a constitutively acting multifunctional serine/threonine kinase, a role of which has been marked in several physiological pathways, making it a potential target for the treatment of many diseases, including Type-II diabetes and Alzheimer’s. Design of GSK-3β selective inhibitor was the key challenge which led to the use of rational approaches like structure based methods (molecular docking Read More

Viruses have been found to exhibit protein kinase activity associated with their purified viral particles. HIV-1 virus particles possess a novel 72 kD protein, Topoisomerase II beta kinase (Topo IIβKHIV) activity. The enzyme, isolated and purified from PEGprecipitated HIV-1 particles, is insensitive against a diverse set of known kinase inhibitors. The pyridine derivatives were found to be active against both Topo IIβKHIV activity and Read More

The ease of access to virtual screening (VS) software in recent years has resulted in a large increase in literature reports. Over 300 publications in the last year report the use of virtual screening techniques to identify new chemical matter or present the development of new virtual screening techniques. The increased use is accompanied by a corresponding increase in misuse and misinterpretation of virtual screening results. Read More