English

Abstract

Introduction Drug discovery and development is an intense, lengthy and an interdisciplinary venture. Recently, a trend towards the use of in-silico chemistry and molecular modelling for computer-aided drug design has gained significant momentum. Insilico drug design skills are used in nanotechnology, molecular biology, biochemistry etc. The main benefit of the in-silico drug design is cost effective in research and development of drugs. There are wide ranges of software that are used in in-silico drug design, Grid computing, window based general PBPK/PD modelling software, PKUDDS for structure based drug design, APIS, JAVA, Perl and Python, in-silico drug design as well as software including software libraries. There are different techniques used in in-silico drug design visualization, homology, molecular dynamic, energy minimization molecular docking and QSAR etc. In-silico drug design can take part considerably in all stages of drug development from the preclinical discovery stage to late stage clinical development. Its exploitation in drug development helps in the selection of only a potent lead molecule and may thus thwart the late stage clinical failures; thereby a major diminution in cost can be achieved. This article gives an insight into all the aspects of in-silico drug design; its potential, drivers, current development and the future prospects. Conclusion In-silico methods have been of great importance in target identification and in prediction of novel drugs. Introduction Drug discovery and development is a very complicated, time consuming process and there are many factors responsible for the failure of different drugs such as lack of effectiveness, side effects, poor pharmacokinetics, and marketable reasons. The expenditure of this process has amplified ominously during the past thirty-four years. The Pharmaceutical Manufacturer’s Association received the industry average reports which have shown that the expenditure of drug development has enlarged from $4 million in 1962 to over $350 million in 1996. The improvement time of a drug from the first synthesis to its foreword in the market, has almost multiplied between 1960 and 1980. It has kept on comparatively unaffected since 1980 with a present time period of 9-13 years.1,4 According to pharmaceutical research and manufacturers the estimated cost of the complete drug discovery process is about US$880 million and takes up to 14 years from initial research stage to the successful marketing of an new drug in 2001.4 The recent figures of DiMasi at the Tufts Centre for Study of Drug Development (CSDD) is about US$802 million spread over 12 years, which was reported in 2003,4 while the Boston Consulting Group estimates the cost as $880 million over 15 years. At present the cost involved in the drug discovery process ranges f rom $800 million to $1.8 billion,5 The establishment of the Computer-Aided Drug Design (CADD) Centre was to endorse joint research among the scientists of various fields like biology, biophysics, structural biology and computational scientists.6 The main objective of CADDC entries is to start these partnerships that lead to the implementation of research projects to discover new compounds with the potential to be transformed into new therapeutic agents. The in-silico drug design is a vast field in which the different sides of basic research and practice are combined and inspire each other,7 modern techniques such as QSAR/QSPR, structure-based design, combinatorial library design, cheminformatics, bioinformatics and the increasing number of biological and chemical databases are used in the field. Furthermore, large numbers of the available tools provide a much developed basis for the design of ligands and inhibitors with preferred specificity.8 The aim of this review was to discuss the process of In-silico drug design.