Strategies in the Rational Drug Design

T.      Mavromoustakos; S.      Durdagi; C.      Koukoulitsa; M.      Simcic; M.      G. Papadopoulos; M.      Hodoscek; S.      Golic Grdadolnik

doi:10.2174/092986711795933731

Abstract

Rational design is applied in the discovery of novel lead drugs. Its rapid development is mainly attributed to the tremendous advancements in the computer science, statistics, molecular biology, biophysics, biochemistry, medicinal chemistry, pharmacokinetics and pharmacodynamics experienced in the last few decades. The promising feature that characterizes the application of rational drug design is that it uses for developing potential leads in drug discovery all known theoretical and experimental knowledge of the system under study. The utilization of the knowledge of the molecular basis of the system ultimately aims to reduce human power cost, time saving and laboratory expenses in the drug discovery. In this review paper various strategies applied for systems which include: (i) absence of knowledge of the receptor active site; (ii) the knowledge of a homology model of a receptor, (iii) the knowledge of the experimentally determined (i.e. X-ray crystallography, NMR spectroscopy) coordinates of the active site of the protein in absence and (iv) the presence of the ligand will be analyzed.

Keywords: Rational drug design, cannabinoid, fullerene, antileukemic steroids, molecular docking, MD simulations, 3D QSAR, molecular biology, biophysics, biochemistry, medicinal chemistry, pharmacokinetics