Paper Citing NAMD - Abstract
Wang, Qianqian; Guo, Jingjing; Jiao, Pingzu; Liu, Huanxiang; Yao, Xiaojun
Exploring the Influence of EGCG on the beta-Sheet-Rich Oligomers of Human Islet Amyloid Polypeptide (hIAPP(1-37)) and Identifying Its Possible Binding Sites from Molecular Dynamics Simulation
PLOS ONE, 9 Art. No. e94796, APR 16 2014
EGCG possesses the ability of disaggregating the existing amyloid fibrils which were associated with many age-related degenerative diseases. However, the molecular mechanism of EGCG to disaggregate these fibrils is poorly known. In this work, to study the influence of EGCG on the full-length human islet amyloid polypeptide 1-37 (hIAPP(1-37)) oligomers, molecular dynamics simulations of hIAPP(1-37) pentamer and decamer with EGCG were performed, respectively. The obtained results indicate that EGCG indeed destabilized the hIAPP(1-37) oligomers. The nematic order parameter and secondary structure calculations coupled with the free-energy landscape indicate that EGCG broke the initial ordered pattern of two polymers, greatly reduced their beta-sheet content and enlarged their conformational space. On this basis, three possible target sites were identified with the binding capacity order of S1>S2>S3. After a deeper analysis of each site, we found that S1 was the most possible site on which residues B-Ile26/Ala25, A-Phe23, B/C-Leu27 and E-Tyr37 played an important role for their binding. The proposal of this molecular mechanism can not only provide a prospective interaction figure between EGCG and beta-sheet-rich fibrils of hIAPP(1-37), but also is useful for further discovering other potential inhibitors.
