Protein Flexibility: A Challenging Issue of Drug Discovery

Author(s): Satya P. Gupta*.

Journal Name: Current Chemical Biology

Volume 12 , Issue 1 , 2018

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Graphical Abstract:


Background: Now-a-days, drug design is an important area of research in medicinal chemistry and theoretical aspects of it basically involve molecular docking. Therefore, a detailed knowledge of drug targets, de facto of proteins/enzymes, is essential and thus it has created interest in the study of protein structure and its flexible nature.

Objective: The article aims to describe in detail the flexible nature of proteins and its implication in drug design.

Method: A detailed survey of the studies on protein flexibility has been made and critically reviewed.

Results: Proteins have been found to possess conformational flexibility. They possess an ensemble of conformations. Now the theory of protein-ligand binding has greatly shifted from lock-and-key model to induced-fit model. Since the current concept assumes that protein can exist in many conformations, a ligand can bind to any conformation depending upon its shape and size and thus ligand of any size can be considered to interact with the protein.

Conclusion: Protein flexibility stands out to be one of the most important and challenging issues for binding and discovering the potent drugs. Proteins may possess several conformations, but to study the nature of the binding site in them, one must consider its binding partner. Thus, only that conformation of protein is involved in the binding in which the structure of binding site is complementary to that of ligand.

Keywords: Protein flexibility, conformational changes, drug targets, docking, catalytic domain, catalytic residues.

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Article Details

Year: 2018
Page: [3 - 13]
Pages: 11
DOI: 10.2174/2212796812666180524100212

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