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- W3029779626 endingPage "1826" @default.
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- W3029779626 abstract "The β-amyloid cleaving enzyme 1 (BACE1) has been thought to be an efficient target for treatment of Alzheimer's disease (AD). Deep insight into inhibitor-BACE1 binding mechanism is of significance for design of potent drugs toward BACE1. In this work, multiple replica accelerated molecular dynamics (MR-aMD) simulations, principal component (PC) analysis, and free energy landscapes were integrated to decode the effect of disulfide bonds (SSBs) in BACE1 on bindings of three inhibitors 3KO, 3KT, and 779 to BACE1. The results from cross-correlation analysis suggest that the breaking of SSBs exerts significant influence on structural flexibility and internal dynamics of inhibitor-bound BACE1. PC analysis and free energy landscapes reveal that the breaking of SSBs not only evidently induces the conformational rearrangement of BACE1 but also highly changes binding poses of three inhibitors in BACE1 and leads to more disordered binding of three inhibitors to BACE1, which is further supported by the increase in binding entropy of inhibitors to BACE1 due to the breaking of SSBs. Residue-based free energy decomposition method was utilized to evaluate contributions of separate residues to inhibitor-BACE1 binding. The results suggest that although the breaking of SSBs in BACE1 does not destroy the interaction network of inhibitors with BACE1 it changes interaction strength of some residues with inhibitors. Meanwhile, the information from residue-based free energy decomposition indicates that residues L91, S96, V130, Y132, Q134, W137, F169, I171, and I179 can be used as efficient targets of drug design toward BACE1." @default.
- W3029779626 created "2020-06-05" @default.
- W3029779626 creator A5021816004 @default.
- W3029779626 creator A5046597133 @default.
- W3029779626 creator A5047318350 @default.
- W3029779626 creator A5054103732 @default.
- W3029779626 date "2020-05-27" @default.
- W3029779626 modified "2023-10-17" @default.
- W3029779626 title "Effects of Disulfide Bonds on Binding of Inhibitors to β-Amyloid Cleaving Enzyme 1 Decoded by Multiple Replica Accelerated Molecular Dynamics Simulations" @default.
- W3029779626 cites W1178456644 @default.
- W3029779626 cites W1616122655 @default.
- W3029779626 cites W1901276796 @default.
- W3029779626 cites W1968984443 @default.
- W3029779626 cites W1975734016 @default.
- W3029779626 cites W1976499671 @default.
- W3029779626 cites W1977040129 @default.
- W3029779626 cites W1978367874 @default.
- W3029779626 cites W1992899488 @default.
- W3029779626 cites W1995089645 @default.
- W3029779626 cites W1995839193 @default.
- W3029779626 cites W2012918940 @default.
- W3029779626 cites W2014772558 @default.
- W3029779626 cites W2016991826 @default.
- W3029779626 cites W2018633278 @default.
- W3029779626 cites W2024376582 @default.
- W3029779626 cites W2025116694 @default.
- W3029779626 cites W2029667189 @default.
- W3029779626 cites W2030456541 @default.
- W3029779626 cites W2030473306 @default.
- W3029779626 cites W2034504333 @default.
- W3029779626 cites W2035687084 @default.
- W3029779626 cites W2036508367 @default.
- W3029779626 cites W2037535298 @default.
- W3029779626 cites W2040091896 @default.
- W3029779626 cites W2042600422 @default.
- W3029779626 cites W2042924462 @default.
- W3029779626 cites W2043666236 @default.
- W3029779626 cites W2050142805 @default.
- W3029779626 cites W2054788798 @default.
- W3029779626 cites W2058151436 @default.
- W3029779626 cites W2062491057 @default.
- W3029779626 cites W2063671284 @default.
- W3029779626 cites W2065462507 @default.
- W3029779626 cites W2067174909 @default.
- W3029779626 cites W2068042361 @default.
- W3029779626 cites W2070013616 @default.
- W3029779626 cites W2072683434 @default.
- W3029779626 cites W2076790509 @default.
- W3029779626 cites W2078304042 @default.
- W3029779626 cites W2081618506 @default.
- W3029779626 cites W2084168484 @default.
- W3029779626 cites W2084972185 @default.
- W3029779626 cites W2088289146 @default.
- W3029779626 cites W2092443343 @default.
- W3029779626 cites W2093034908 @default.
- W3029779626 cites W2095461786 @default.
- W3029779626 cites W2096584150 @default.
- W3029779626 cites W2103325328 @default.
- W3029779626 cites W2105103540 @default.
- W3029779626 cites W2106140689 @default.
- W3029779626 cites W2118233996 @default.
- W3029779626 cites W2129521473 @default.
- W3029779626 cites W2131819352 @default.
- W3029779626 cites W2132720896 @default.
- W3029779626 cites W2140514518 @default.
- W3029779626 cites W2144519630 @default.
- W3029779626 cites W2144775933 @default.
- W3029779626 cites W2146879721 @default.
- W3029779626 cites W2152997175 @default.
- W3029779626 cites W2154755614 @default.
- W3029779626 cites W2159972803 @default.
- W3029779626 cites W2163573957 @default.
- W3029779626 cites W2164270482 @default.
- W3029779626 cites W2166765429 @default.
- W3029779626 cites W2237020303 @default.
- W3029779626 cites W2283762586 @default.
- W3029779626 cites W2297303230 @default.
- W3029779626 cites W2312550920 @default.
- W3029779626 cites W2314905502 @default.
- W3029779626 cites W2325034207 @default.
- W3029779626 cites W2332712348 @default.
- W3029779626 cites W2335200606 @default.
- W3029779626 cites W2342675883 @default.
- W3029779626 cites W2404280981 @default.
- W3029779626 cites W2510299230 @default.
- W3029779626 cites W2530696470 @default.
- W3029779626 cites W2553725768 @default.
- W3029779626 cites W2560771928 @default.
- W3029779626 cites W2598982774 @default.
- W3029779626 cites W2609476392 @default.
- W3029779626 cites W2782438044 @default.
- W3029779626 cites W2783351753 @default.
- W3029779626 cites W2785390464 @default.
- W3029779626 cites W2793665794 @default.
- W3029779626 cites W2795913741 @default.
- W3029779626 cites W2797291909 @default.
- W3029779626 cites W2804603144 @default.
- W3029779626 cites W2810957490 @default.