Protein-Ligand Docking Methodologies and Its Application in Drug Discovery

Protein-Ligand Docking Methodologies and Its Application in Drug Discovery

Sanchaita Rajkhowa (Tezpur University, India) and Ramesh C. Deka (Tezpur University, India)
DOI: 10.4018/978-1-5225-0115-2.ch008


Molecular docking is a key tool in structural biology and computer-assisted drug design. Molecular docking is a method which predicts the preferred orientation of a ligand when bound in an active site to form a stable complex. It is the most common method used as a structure-based drug design. Here, the authors intend to discuss the various types of docking methods and their development and applications in modern drug discovery. The important basic theories such as sampling algorithm and scoring functions have been discussed briefly. The performances of the different available docking software have also been discussed. This chapter also includes some application examples of docking studies in modern drug discovery such as targeted drug delivery using carbon nanotubes, docking of nucleic acids to find the binding modes and a comparative study between high-throughput screening and structure-based virtual screening.
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1. Introduction

Traditionally, the discovery of new drugs has arisen from observations that various plant extracts possess interesting biological effects. However, early users of such plant extracts did not understand or realize which components in the material were responsible for achieving these therapeutic benefits. The main difference between modern and age-old drug discovery is that the identification of the composition of matter, or the active form, within the medicine itself. Drug discovery and development is mostly a complex, expensive, time consuming and market-driven process with very few novel drug candidates actually making it through the Food and Drug Administration (FDA) for approval. Modern drug discovery process involves rational approach with knowledge about enzymes and receptors and the use of complex synthetic methods and technologies such as combinatorial chemistry, microwave assisted organic synthesis and high-throughput (HTS) biological screening methods (Patil, 2012).

In recent years, there has been an increase in the number of new therapeutic targets for modern drug discovery with enormous contribution to many structural details of proteins and protein-ligand complexes. This has been possible as a result of the completion of the human genome project, along with the development of high-throughput protein purification, crystallography and nuclear magnetic resonance spectroscopy. Experimental high-throughput screening (HTS) and combinatorial chemistry were developed in order to overcome the various problems faced by lead discovery in drug development. Some exceptional number of novel leads was anticipated using sophisticated large-scale techniques, which would result in a substantial increase in novel entities launched to the market per year. However, this process had some drawbacks which included lack of validation and further optimization of these compounds into actual leads and preclinical candidates.

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