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Advances in structure based drug design and virtual screening
Author(s) -
Abagyan Ruben
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.720.7
Subject(s) - virtual screening , drug repositioning , g protein coupled receptor , drug , docking (animal) , drug discovery , computer science , drug design , computational biology , rational design , repurposing , pharmacology , receptor , medicine , bioinformatics , biology , ecology , genetics , nursing
The rapid growth of the number of structures in the Protein Data Bank and the emergence of the chemogenomics databases combined with the advances in computational methods created a unique opportunity for a wider application of rational drug design and structure based virtual screening. Another factor is the determination of the three dimensional structure of beta 2 adrenergic receptor. The main challenge, however, remains to be the understanding and treatment of the receptor induced fit effects. We built the largest structural chemogenomic database and presented a docking algorithm that reliably docks ligands to their pockets despite the induced fit effect. The new GPCR structure and its implications for rational design and screening of potent and specific GPCR agonists and antagonists are reviewed. The success of the ligand guided models is demonstrated on several cases studies including drug repurposing. This work was supported by NIH grants 5R01‐GM074832‐02 and 5R01‐GM071872‐02.