期刊
SAR AND QSAR IN ENVIRONMENTAL RESEARCH
卷 31, 期 2, 页码 149-170出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1062936X.2019.1701075
关键词
Bromodomain-containing protein 9; binding free energy; molecular dynamics; principal component analysis; MM-GBSA method
类别
资金
- National Natural Science Foundation on China [11504206]
- Science Foundation of Shandong Jiaotong University [Z201703, Z201202]
Recently, bromodomain-containing protein 9 (BRD9) has been a prospective therapeutic target for anticancer drug design. Molecular dynamics (MD) simulations combined with molecular mechanics generalized Born surface area (MM-GBSA) method were adopted to explore binding modes of three inhibitors (5SW, 5U2, and 5U6) to BRD9 and identify the hot spot of the inhibitor-BRD9 binding. The results indicate that the inhibitor 5SW has the strongest binding ability to BRD9 among the current three inhibitors. Furthermore, the rank of the binding free energies predicted by MM-GBSA approach agrees with that determined by the experimental values. In addition, inhibitor-residue interactions were computed by using residue-based free-energy decomposition method and the results suggest that residue His42 produces the CH-H interactions, residues Asn100, Ile53 and Val49 produce the CH- interactions with three inhibitors and Tyr106, Phe45 and Phe44 generate the pi-pi interactions with inhibitors. Notably, the residue Asn140 forms hydrogen bonding interactions with three inhibitors. This research is expected to provide useful molecular basis and dynamics information at atomic levels for the design of potent inhibitors inhibiting the activity of BRD9.
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