• Structure-based drug design of proteins as a novel therapeutic perspectives
  • Armin Mokhtariye,1 Mohammad Reza Mofid,2,*
    1. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
    2. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran


  • Introduction: Structure-based drug design (SBDD) of protein ligands has emerged as a new tool in medicinal chemistry. The goal of SBDD is to identify a suitable compound for clinical testing (drug candidate) by designing and optimizing of a chemical structure. It is based on knowledge of the drug’s three-dimensional structure and how its shape and charge cause it to interact with its biological target, ultimately eliciting a medical effect. There are numerous drugs available on the market that have been identified by SBDD, as a successful experience; Human immunodeficiency virus (HIV)-1 -inhibiting FDA-approved drugs.
  • Methods: SBDD proceeds through multiple cycles leading an optimized drug candidate to clinical trials. In the first phase, a potential therapeutic target and active ligands are identified. The fundamental step involves cloning of the target gene followed by the extraction, purification, and 3D structure determination of the protein. A complete investigation of the electrostatic properties of the binding site can be performed using a 3D structure of the target molecule. These molecules are ranked according to a scoring system based on electrostatic and steric interactions with the binding site. In the second phase, the top hits are synthesized and optimized. The next step is to determine the 3D structure of the target protein in complex with the promising ligand obtained in the first phase. The third phase includes clinical trials of the lead compounds.
  • Results: Those compounds that pass the clinical trials proceed to the fourth phase in which the drug is distributed in the market for clinical use.
  • Conclusion: In conclusion, bioinformatics offers several approaches for the prediction of structure and function of proteins on the basis of sequence and structural similarities. SBDD has made significant improvements in the structural properties of biomolecules and the rational drug design. Some drugs are as a successful experience that have been identified by SBDD; Human immunodeficiency virus (HIV)-1 -inhibiting drugs. However, despite a lot of improvements and currents developments in SBDD, a consistent solution is yet to be developed.
  • Keywords: Structure-based drug design, 3D structure, Bioinformatics, molecular biology