What is Drug Design ?

Drug discovery and development is an intense, lengthy and an interdisciplinary endeavor. Drug discovery is mostly portrayed as a linear, consecutive process that starts with target and lead discovery, followed by lead optimization and pre-clinical in vitro and in vivo studies to determine if such compounds satisfy a number of pre-set criteria for initiating clinical development. For the pharmaceutical industry, the number of years to bring a drug from discovery to market is approximately 12-14 years and costing upto $1.2 - $1.4 billion dollars. Traditionally, drugs were discovered by synthesizing compounds in a time-consuming multi-step processes against a battery of in vivo biological screens and further investigating the promising candidates for their pharmacokinetic properties, metabolism and potential toxicity. Such a development process has resulted in high attrition rates with failures attributed to poor pharmacokinetics (39%), lack of efficacy (30%), animal toxicity (11%), adverse effects in humans (10%) and various commercial and miscellaneous factors. Today, the process of drug discovery has been revolutionized with the advent of genomics, proteomics, bioinformatics and efficient technologies like, combinatorial chemistry, high throughput screening (HTS), virtual screening, de novo design, in vitroin silicoADMET screening and structure-based drug design.

What is in-silico Drug Design ?

In silico methods can help in identifying drug targets via bioinformatics tools.
They can also be used to analyze the target structures for possible binding/ active sites, generate candidate molecules, check for their drug likeness , dock these molecules with the target , rank them according to their binding affinites , further optimize the molecules to improve binding characteristics

The use of computers and computational methods permeates all aspects of drug discovery today and forms the core of structure-based drug design. High-performance computing, data management software and internet are facilitating the access of huge amount of data generated and transforming the massive complex biological data into workable knowledge in modern day drug discovery process. The use of complementary experimental and informatics techniques increases the chance of success in many stages of the discovery process, from the identification of novel targets and elucidation of their functions to the discovery and development of lead compounds with desired properties. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost. Major roles of computation in drug discovery are; (1) Virtual screening & de novo design, (2) in silicoADME/T prediction and (3) Advanced methods for determining protein-ligand binding

in-silico drug design

Why in-silico Drug Design is significant ?

As structures of more and more protein targets become available through crystallography, NMR and bioinformatics methods, there is an increasing demand for computational tools that can identify and analyze active sites and suggest potential drug molecules that can bind to these sites specifically. Also to combat life-threatening diseases such as AIDS, Tuberculosis, Malaria etc., a global push is essential. Millions for Viagra and pennies for the diseases of the poor is the current situation of investment in Pharma R&D. Time and cost required for designing a new drug are immense and at an unacceptable level. According to some estimates it costs about $880 million and 14 years of research to develop a new drug before it is introduced in the market Intervention of computers at some plausible steps is imperative to bring down the cost and time required in the drug discovery process
Cost involved in Drug Design