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【答案】应助回帖
oven1986: LS-EPI+1, 感谢应助！ 2014-09-05 09:44:59
Theoretical Studies on Binding and Specificity Mechanisms of Farnesyltransferase (FTase) and Geranylgeranyltransferase Type-I (GGTase-I) Inhibitors by Molecular Modeling
作者:Zhou, SR (Zhou, Shirou)
COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING
卷: 17
期: 6
页: 509-519
DOI: 10.2174/1386207317666140120122920
出版年: 2014
查看期刊信息
摘要
Farnesyltransferase (FTase) and geranylgeranyltransferase type-I (GGTase-I) are two members of protein prenyltransferases, which play critical roles in lipid post-translational modifications. Potent inhibitors of FTase and GGTase-I have been confirmed to show favorable influence on the therapies of various diseases, such as cancers, malaria and Toxoplasmosis. However, designing highly specific inhibitors toward FTase or GGTase-I without influencing their binding affinity remains a big challenge. In this work, molecular docking, molecular dynamics (MD) simulations and MM/GBSA free energy calculations were employed to study the bindings of two highly selective inhibitors (lonafarnib and GGTI-2133) towards FTase or GGTase-I. The specificities of the studied inhibitors derived from the predicted binding free energies are consistent with the experimental data. The analysis of the energetic components illustrates that both the non-polar and polar interactions play critical roles in determining the specificity between FTase and GGTase-I. Moreover, the protein-inhibitor interaction spectra for the studied inhibitors were determined through the decomposition of the binding free energies, and the important residues for binding and specificity were highlighted. Our study provides useful information for the rational design of selective FTase or GGTase-I inhibitors.
关键词
作者关键词:Free energy decomposition; FTase; GGTase-I; MM/GBSA; molecular docking; molecular dynamics simulations; Prenyltransferase; specificity
KeyWords Plus:FREE-ENERGY CALCULATIONS; PEPTIDE INTERACTION INTERFACE; CHRONIC MYELOID-LEUKEMIA; INDUCED LUNG-CANCER; PROTEIN FARNESYLTRANSFERASE; DRUG-RESISTANCE; FORCE-FIELD; HETEROLOGOUS EXPRESSION; DYNAMICS SIMULATIONS; TRYPANOSOMA-BRUCEI
作者信息
通讯作者地址: Zhou, SR (通讯作者)
Yueyang Vocat Tech Coll, Dept Basic Med, Yueyang 414000, Hunan, Peoples R China.
地址:
[ 1 ] Yueyang Vocat Tech Coll, Dept Basic Med, Yueyang 414000, Hunan, Peoples R China
电子邮件地址:shirouzhou@126.com
出版商
BENTHAM SCIENCE PUBL LTD, EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES
类别 / 分类
研究方向:Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy
Web of Science 类别:Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy
文献信息
文献类型:Article
语种:English
入藏号: WOS:000338848600004
ISSN: 1386-2073
电子 ISSN: 1875-5402
期刊信息
Impact Factor (影响因子): Journal Citation Reports®
其他信息
IDS 号: AL0WU
Web of Science 核心合集中的 "引用的参考文献": 71
Web of Science 核心合集中的 "被引频次": 0 |
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