Abstract
In silico tools have indeed reframed the steps involved in traditional drug discovery and development process and the term in silico has become a familiar term in pharmaceutical sector like the terms in vitro and in vivo. The successful design of HIV protease inhibitors, Saquinavir, Indinavir and other important medicinal agents, initiated interest of researchers in structure based drug design approaches (SBDD). The interactions between biomolecules and a ligand, binding energy, free energy and stability of biomolecule-ligand complex can be envisioned and predicted by applying molecular docking studies. Protein-ligand, protein-protein, DNA-ligand interactions etc. aid in elucidating molecular level mechanisms of drug molecules. In the Ligand based drug design (LBDD) approaches, QSAR studies have tremendously contributed to the development of antimicrobial, anticancer, antimalarial agents. In the recent years, multiQSAR (mt-QSAR) approaches have been successfully employed for designing drugs against multifactorial diseases. Output of a research in several instances is rewarding when both SBDD and LBDD approaches are combined. Application of in silico studies for prediction of pharmacokinetics was once a real challenge but one can see unlimited number publications comprising tools, data bases which can accurately predict almost all the pharmacokinetic parameters. Absorption, distribution, metabolism, transporters, blood brain barrier permeability, hERG toxicity, P-gp affinity and several toxicological end points can be accurately predicted for a candidate molecule before its synthesis. In silico approaches are greatly encouraged a result of growing limitations and new legislations related to the animal use for research. The combined use of in vitro data and in silico tools will definitely decrease the use of animal testing in the future.In this chapter, in silico approaches and their applications are reviewed and discussed giving suitable examples.
Structure-based drug design of a new chemical class of small molecules active against influenza A nucleoprotein in vitro and in vivo