Predicition of relative stability between TACE/gelastatin and TACE/gelastatin hydroxamate

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Title
Predicition of relative stability between TACE/gelastatin and TACE/gelastatin hydroxamate
Author(s)
G Y Nam; G Han; Hwan Mook Kim; K T No
Bibliographic Citation
Bulletin of Korean Chemical Society, vol. 31, no. 11, pp. 3291-3296
Publication Year
2010
Abstract
A gelastatins (1), natural MMP inhibitors, and their hydroxamate analogues (2) in TACE enzyme evaluated for discovery of potent TACE inhibitors. We have employed molecular dynamics simulations to compute the relative free energy of hydration and binding to TACE for gelastatin (1) and its hydroxamate analogue (2). The relative free energy difference is directly described in this article using the free energy perturbation approach as a means to accurately predict the TACE inhibitor of gelastatin analogues. The results show that the good agreement between the experimental and theoretical relative free energies of binding, gelastatin hydroxamate (2) binds stronger to TACE by ?3.37 kcal/mol. The desolvation energy costs significantly reduced binding affinity, hydroxamate group associated with high desolvation energy formed strong favorable interactions with TACE with more than compensated for the solvation costs and therefore led to an improvement in relative binding affinity.
Keyword
Rheumatoid ArthritisTACEZn-binding anchorGelastatinFree energy perturbation
ISSN
0253-2964
Publisher
Wiley
DOI
http://dx.doi.org/10.5012/bkcs.2010.31.11.3291
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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