Application of Docking for Lead Optimization

Abstract Lead optimization is a process for improving a hit or a lead compound to design drug candidates with improved efficacy and drug-like properties. Advancements in molecular structure determination and computational techniques have significantly boosted lead optimization process. Molecular docking has emerged as a reliable and cost-effective technique for lead identification and optimization using computational methods. Computational tools with advanced scoring functions utilizing artificial intelligence improve predictions. However, despite the advances in computational techniques, the success is limited and further improvement in these tools is required to simulate the complex biological environments. In this chapter, we will discuss applications of molecular docking for lead optimization in drug discovery. Applications based on molecular mechanics, thermodynamics and kinetics profiling, relative free binding energies, and toxicology predictions for optimization of lead molecules are highlighted.