A. Srinivas Reddy

Virtual Screening in Drug Discovery - A Computational Perspective †

Virtual screening emerged as an important tool in our quest to access novel drug like compounds. There are a wide range of comparable and contrasting methodological protocols available in screening databases for the lead compounds. The number of methods and software packages which employ the target and ligand based virtual screening are increasing at a rapid pace. However, the general understanding on the applicability and limitations of these methodologies is not emerging as fast as the developments of various methods. Therefore, it is extremely important to compare and contrast various protocols with practical examples to gauge the strength and applicability of various methods. The review provides a comprehensive appraisal on several of the available virtual screening methods to-date. Recent developments of the docking and similarity based methods have been discussed besides the descriptor selection and pharmacophore based searching. The review touches upon the application of statistical, graph theory based methods machine learning tools in virtual screening and combinatorial library design. Finally, several case studies are undertaken where the virtual screening technology has been applied successfully. A critical analysis of these case studies provides a good platform to estimate the applicability of various virtual screening methods in the new lead identification and optimization.

Cation-aromatic database.

Cation–aromatic database (CAD) is a publicly available web‐based database that aims to provide further understanding of interaction between a cation and the π interactions. A tool to identify the interactions in a user‐given protein is also added to the database. CAD is freely accessible via the Internet at http://203.199.182.73/gnsmmg/databases/cad/ Proteins 2007.

Short Communication: Protein ligand interaction database (PLID)

A comprehensive database named, protein ligand interaction database (PLID), is created with 6295 ligands bound to proteins extracted from the protein data bank (PDB). This is by far the most comprehensive database of physico-chemical properties, quantum mechanical descriptors and the residues present in the active site of proteins. It is a publicly available web-based database (via the Internet) at http://203.199.182.73/gnsmmg/databases/plid/.

Towards design of the smallest planar tetracoordinate carbon and boron systems

A series of cyclic hydrocarbons analogs where a carbon displays unusual planar tetracoordinate structure is proposed, employing hybrid density functional theory calculations using B3LYP functional and 6‐311+G** basis set. Various strategies were employed to design the neutral planar tetracoordinate hydrocarbon analogs. The same strategy is employed for designing the planar tetracoordinate boron systems. The simplest neutral planar tetracoordinate hydrocarbons were proposed and the effect of substitution on their stability has been assessed. The aromatic stabilization is gauged with nucleus independent chemical shift calculations. The activation barriers for the ring opening reaction, the highest occupied molecular orbital and lowest unoccupied molecular orbitals gap and singlet‐triplet energy difference were estimated to gauge the plausibility experimental realization.

The network of receptors characterize B cell receptor micro- and macroclustering in a Monte Carlo model.

During the recognition of soluble antigens, B cell receptors (BCR) are known to form signaling clusters that can crucially modulate intracellular activation pathways and B cell response. Little is known about the precise nature of receptor cluster and its formation mechanism for the case of soluble antigens. Initial experiments have shown that B cell receptors first microcluster upon ligation with soluble antigens, and then coarsen into a macroscopic cap structure at one pole of a B cell. Such a mutual receptor-receptor attraction can arise locally due to cross-linking by soluble antigens among other possibilities. We develop an energy based Monte Carlo model to investigate the mechanism of B-cell receptor clustering upon ligation with soluble antigens. Our results show that mutual attraction between nearest neighbor receptor pairs can lead to microclustering of B cell receptors, but it is not sufficient for receptor macroclustering. A simple model of biased diffusion where BCR molecules experience a biased directed motion toward the largest cluster is then applied, which results in a single macrocluster of receptor molecules. The various types of receptor clusters are analyzed using the developed network-based metrics such as the average distance between any pairs of receptors.

A Practical Total Synthesis of (+)-Spirolaxine Methyl Ether

An efficient and practical total synthesis of (+)-spirolaxine methyl ether is described. The phthalide-aldehyde 3 has been prepared via the Diels-Alder reaction between 1,4-unconjugated diene 5 and a long-chain acetylenic dienophile 6. The carbon framework of spiroketal sulfone 4 has been constructed from monobenzyl protected 1,5-pentanediol and the stereochemistry in both the phthalide portion and the spiroketal portion has been established by the Sharpless asymmetric epoxidation.