In Silico Modeling and its Applications on Biomolecules: Computational Studies on Cholinesterase and Other Medicinally Important Enzymes

The book provides a general introduction to advanced computational techniques applied in various stages of drug discovery. In particular, it focuses on molecular modeling, ligand- and structure-based drug design methods, and data mining in chemical informatics. Application side of this book deals with the development of the first structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) model of butyrylcholinesterase - a putative drug target for the treatment of Alzheimer's disease. The other part is comprised of detailed work conducted on 5-HT2C agonists. It describes pharmacophore modeling and 3D-QSAR studies. Comparative Molecular Field Analysis coupled with a genetic algorithm (CoMFA-GA) was carried out for aligned ligands. The last part describes the drug target MTB-Thymidine monophosphate kinase (TMPKMtub). The molecular modeling analyses resulted in identification of a cluster of water molecules that mediate key interactions between bound ligands and backbone atoms of the enzyme residues.

Reaz Uddin holds a PhD degree in the field of computational medicinal chemistry. Currently he is working as junior faculty at Dr. Panjwani Center for Molecular Medicine, ICCBS, University of Karachi. His particular area of interest includes the use of computational biology methods to understand complex biological phenomena.