期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 39, 期 17, 页码 6440-6451出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1799863
关键词
Amyloid-beta peptide; small molecular inhibitor; molecular dynamics simulation
资金
- National Natural Science Foundation of China [21908165, 21878234, 21576199]
- Natural Science Foundation of Tianjin from the Tianjin Municipal Science and Technology Commission [18JCZDJC33000]
- project of Novel Coronavirus Prevention and Treatment of Tianjin University of Science Technology [2020STCV0018]
- Open Project Program of State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science Technology [SKLFNS-KF-201902]
This study utilized molecular dynamics simulations to investigate the inhibitory effects of HCP on the conformational transformation of A beta. The results showed that HCP can prevent the conformational transition of A beta monomers in a concentration-dependent manner, suggesting its potential as an anti-A beta compound.
Previous studies have indicated that 5-hydroxycyclopenicillone (HCP), an active compound derived from marine sponge, could inhibit oligomerization of amyloid beta-protein (A beta). However, the molecular basis for the interaction between HCP and A beta remains unclear. Herein, all-atom molecular dynamics (MD) simulations were used to explore the conformational conversion of an A beta(40) monomer at different concentrations (0-40 mM) of HCP at the atomic level. It is confirmed that the conformational transition of the A beta(40) monomer is prevented by HCP in a concentration-dependent mannerin silico. In 40 mM HCP solution, the initial alpha-helix-rich conformation of A beta(40) monomer is kept under the action of HCP. The intra-peptide hydrophobic collapse and D23-K28 salt bridge are prevented by HCP. Moreover, it is indicated that the non-polar binding energy dominates the binding between HCP and A beta(40) monomer as evaluated by molecular mechanics Poisson-Boltzmann surface area method. And, the residues of F4, Y10, V12, L17 and L34 in A beta(40) might contribute to the binding energy in HCP-A beta(40) complex. All these results elucidate the molecular mechanism underlying the inhibitory effects of HCP against the conformational transformation of A beta(40), providing a support that HCP may be developed as a potential anti-A beta compound for the treatment of A beta-related diseases.
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