Molecular Dynamics Simulation in Drug Discovery: Opportunities and Challenges

Drug discovery is the process used to discover new candidate medications. In the past, most drugs were discovered by identification of active-ingredients or by serendipity. Modern drug discovery is more focused and streamlined. It starts with target identification, followed by the identification of inhibitors that bind to the target and inhibit its activity. However, developing a new drug takes typically 10–12 years before it can be commercialized. Furthermore, drug discovery costs can range between several hundred million to billions of US dollars. Recent progresses in computational approaches have sped up drug discovery and development research. Computer-aided drug design (CADD) speeds up the hit-to-lead process and enables compounds to pass the barriers of preclinical testing in a short time. Molecular dynamics (MD) simulation has emerged as an important tool in the study of the conformational flexibility and dynamics of drug-target complexes. MD simulation helps to replicate the biological events in a computer simulation. It has become a routine computational tool for CADD and a revolution in the field of drug development. It provides an accurate estimate of thermodynamics and kinetics associated with drug-target interaction and binding. Development of new methods, software, and hardware has boosted the use of MD simulation among scientists working with CADD as well as in biopharmaceutical industry. Improvements in the force-field methods may further enhance the accuracy of free-energy predictions.