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.
| Original language | English |
|---|---|
| Pages (from-to) | 3291-3296 |
| Number of pages | 6 |
| Journal | Bulletin of the Korean Chemical Society |
| Volume | 31 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2010 Nov 20 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
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Prediction of relative stability between TACE/gelastatin and TACE/gelastatin hydroxamate. / Nam, Ky Youb; Han, Gyoonhee; Kim, Hwan Mook; No, Kyoung Tai.
In: Bulletin of the Korean Chemical Society, Vol. 31, No. 11, 20.11.2010, p. 3291-3296.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prediction of relative stability between TACE/gelastatin and TACE/gelastatin hydroxamate
AU - Nam, Ky Youb
AU - Han, Gyoonhee
AU - Kim, Hwan Mook
AU - No, Kyoung Tai
PY - 2010/11/20
Y1 - 2010/11/20
N2 - 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.
AB - 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.
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U2 - 10.5012/bkcs.2010.31.11.3291
DO - 10.5012/bkcs.2010.31.11.3291
M3 - Article
VL - 31
SP - 3291
EP - 3296
JO - Bulletin of the Korean Chemical Society
JF - Bulletin of the Korean Chemical Society
SN - 0253-2964
IS - 11
ER -