Identification Of Potent Agonists Of The Longevity Gene Sirtuin-1 From Traditional Chinese Medicine Database

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Title:	Identification Of Potent Agonists Of The Longevity Gene Sirtuin-1 From Traditional Chinese Medicine Database
Authors:	Jian, Yi-Ru
Contributors:	Department of Biomedical informatics Chen, Calvin Yu-Chian
Keywords:	traditional Chinese medicine (TCM);molecular dynamics (MD);Sirtuin-1 (SIRT1);longevity geine;anti-aging
Date:	2012
Issue Date:	2012-11-18 08:08:17 (UTC+0)
Publisher:	Asia University
Abstract:	Silent information regulator 1 (SIRT1) is a class III nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase. The demonstrated anti-aging properties of SIRT1 make it a desirable target for anti-aging drugs. We employed compounds downloaded from Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan ； http://tcm.cmu.edu.tw/) for virtual screening potent agonists of SIRT1. Docking results indicate that TCM candidates, (S)-tryptophan-betaxanthin, 5-O-feruloylquinic acid, and RosA, have higher Dock Scores than the control, Cambinol, and that His363 and Ser442 are key binding residues. Direct interaction with His363 was observed in all but 5-O-feruloylquinic acid. During molecular dynamics (MD) simulation, additional stabilizing bonds were formed by the TCM candidates. (S)-Tryptophan-betaxanthin maintained binding with His363 and Ser442, and formed new interactions with Phe273, Arg274, and Leu443. 5-O-Feruloylquinic acid formed H-bonds with His363 and Lys444. RosA formed stable interactions with Phe273, Arg274, and Lys412 in addition to the original H-bond with Ser442. Hence, we observed different binding H-bonds between the results of molecular dynamics and docking. Structurally, carboxylic groups of the TCM candidates are critical for forming stable interactions. Not only does the carboxylic group directly bind to His363, but it also increases affinity with SIRT1 by H-bond formation with residues Ser441-Lys444. (S)-Tryptophan-betaxanthin, 5-O-feruloylquinic acid and RosA might be potent agonists for SIRT1 that can be applied in developing longevity drugs.
Appears in Collections:	[生物資訊與醫學工程學系 ] 博碩士論文

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