TY - JOUR
T1 - Molecular mechanism of ligand bindings to Zika virus at SAM site
AU - Liu, Xiao
AU - Zhao, Yang
AU - Zhang, John Z.H.
N1 - Funding Information:
This work was supported by National Key R&D Program of China (Grant no. 2016YFA0501700), National Natural Science Foundation of China (Grant nos. 21433004, 91753103), Singapore Ministry of Education Academic Research Fund Tier 1 (Grant Nos. 2-17-T1-001-161, 2018-T1-002-172), Innovation Program of Shanghai Municipal Education Commission (201701070005E00020), Shanghai University of Engineering Science research start-up fund (no. 0244-E3-0507-19-05203) and NYU Global Seed Grant. JZ acknowledges the support of NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the ECNU Public Platform for Innovation 001 for providing supercomputer time.
Funding Information:
This work was supported by National Key R&D Program of China (Grant no. 2016YFA0501700 ), National Natural Science Foundation of China (Grant nos. 21433004 , 91753103 ), Singapore Ministry of Education Academic Research Fund Tier 1 (Grant Nos. 2-17-T1-001-161 , 2018-T1-002-172 ), Innovation Program of Shanghai Municipal Education Commission ( 201701070005E00020 ), Shanghai University of Engineering Science research start-up fund (no. 0244-E3-0507-19-05203 ) and NYU Global Seed Grant. JZ acknowledges the support of NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the ECNU Public Platform for Innovation 001 for providing supercomputer time.
Publisher Copyright:
© 2019
PY - 2019/11/16
Y1 - 2019/11/16
N2 - We investigated residue-specific binding free energies using computational alanine scanning with interaction entropy method to identify hot-spots and unravel molecular basis in 3 ligand bindings to Zika SAM binding site. This approach allows one to obtain quantitatively residue-specific contributions to protein-ligand binding free energy. Our computational analysis identified four major residues, W87, I147, H110, and K105 that contribute most to the ZIKV bindings to both SAH and SFG ligands. There are two additional residues, R160 and R163, that also contribute significantly to the binding. Finally, the computed total binding free energies are in good agreement with experimentally measured data.
AB - We investigated residue-specific binding free energies using computational alanine scanning with interaction entropy method to identify hot-spots and unravel molecular basis in 3 ligand bindings to Zika SAM binding site. This approach allows one to obtain quantitatively residue-specific contributions to protein-ligand binding free energy. Our computational analysis identified four major residues, W87, I147, H110, and K105 that contribute most to the ZIKV bindings to both SAH and SFG ligands. There are two additional residues, R160 and R163, that also contribute significantly to the binding. Finally, the computed total binding free energies are in good agreement with experimentally measured data.
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U2 - 10.1016/j.cplett.2019.136771
DO - 10.1016/j.cplett.2019.136771
M3 - Article
AN - SCOPUS:85072300691
SN - 0009-2614
VL - 735
JO - Chemical Physics Letters
JF - Chemical Physics Letters
M1 - 136771
ER -