De Novo Ligand Design to Partially Flexible Active Sites: Application of the ReFlex Algorithm to Carboxypeptidase A, Acetylcholinesterase, and the Estrogen Receptor

Citations Over TimeTop 10% of 2008 papers

Abstract

Reflex is a recent algorithm in the de novo ligand design software, SkelGen, that allows the flexibility of amino acid side chains in a protein to be taken into account during the drug-design process. In this paper the impact of flexibility on the solutions generated by the de novo design algorithm, when applied to carboxypeptidase A, acetylcholinesterase, and the estrogen receptor (ER), is investigated. The results for each of the targets indicate that when allowing side-chain movement in the active site, solutions are generated that were not accessible from the multiple static protein conformations available for these targets. Furthermore, an analysis of structures generated in a flexible versus a static ER active site suggests that these additional solutions are not merely noise but contain many interesting chemotypes.

Related Papers

• → Myrtenal inhibits acetylcholinesterase, a known Alzheimer target(2011)76 cited
• → The Effects of Exercise-induced Fatigue on Acetylcholinesterase Expression and Activity at Rat Neuromuscular Junctions(2009)15 cited
• → Quaternary Heteroarenium Salts as the Competitive Inhibitors of the Brain Acetylcholinesterase(2004)15 cited
• Molecular forms of hippocampal acetylcholinesterase and their changes following septal lesions in the rat.(1991)
• Acetylcholinesterase 정성검사에 용혈 검체가 미치는 영향(2015)