Abstract：
:The binding mode of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-ami dino-2- naphthyl)propanoic acid hydrochloride (DX-9065a, 4) to Factor Xa is examined using inhibition data for a series of analogs that have a hydrophobic group as well as basic or dibasic functionality. Comparative molecular field analysis is utilized on a series of DX-9065a analogs in a series of proposed alternative binding modes. A quantitative measure is provided that distinguishes between the proposed binding modes that describes 'how well' the binding mode explains the structure-activity relationship or the best 3D QSAR agrees with the crystallographically determined binding mode. The best model is in agreement with recently available data [Brandstetter et al., J. Biol. Chem., 271 (1996) 29988]. The highest statistical correlation occurs with the second basic group accommodated in the vicinity of Glu97 and a hydrophobic group accommodated in the pocket defined by Phe174, Tyr99 and Trp215. Also, the best model arises when the conformation of the Glu97 side chain is modified such that an H-bond interaction is maintained with the inhibitor if possible. The model also shows a tightening of the S1 pocket as is shown in the recent data described above.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Vaz RJ,McLean LR,Pelton JTdoi
10.1023/a:1007969517376subject
Has Abstractpub_date
1998-03-01 00:00:00pages
99-110issue
2eissn
0920-654Xissn
1573-4951journal_volume
12pub_type
杂志文章abstract：:We have derived a model of the nicotinic acetylcholine binding site. This was accomplished by using three known agonists (acetylcholine, nicotine and epibatidine) as templates around which polypeptide side chains, found to be part of the receptor cavity from published molecular biology studies, are allowed to flow fre...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008029924865
更新日期：1999-01-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129749
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/BF00117278
更新日期：1995-02-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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更新日期：2014-03-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000030037.67742.cb
更新日期：2004-02-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9880-1
更新日期：2015-12-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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更新日期：2014-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-014-9823-2
更新日期：2015-05-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008184403558
更新日期：2000-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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更新日期：2019-02-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000047812.39758.ab
更新日期：2004-05-01 00:00:00
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更新日期：2020-10-26 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9759-6
更新日期：2014-11-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9420-6
更新日期：2011-05-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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更新日期：2021-01-04 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125314
更新日期：1990-06-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
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更新日期：1987-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007973008558
更新日期：1998-01-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
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更新日期：2017-09-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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更新日期：2019-05-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
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更新日期：2011-08-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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更新日期：2009-03-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0176-0
更新日期：2019-01-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125172
更新日期：1995-08-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9886-8
更新日期：2016-01-01 00:00:00
