TY - JOUR
T1 - Determination of binding affinities of 3-Hydroxy-3-Methylglutaryl Coenzyme A reductase inhibitors from free energy calculation
AU - Sun, Zhaoxi
AU - Wang, Xiaohui
AU - Zhang, John Z.H.
N1 - Funding Information:
This work was supported China Scholarship Council and National Key R&D Program of China (Grant no. 2016YFA0501700). Computer access to the CLAIX cluster of RWTH Aachen University and clusters of Forschungszentrum Juelich is gratefully acknowledged. We thank anonymous reviewers for valuable comments and critical reading.
Funding Information:
This work was supported China Scholarship Council and National Key R&D Program of China (Grant no. 2016YFA0501700). Computer access to the CLAIX cluster of RWTH Aachen University and clusters of Forschungszentrum Juelich is gratefully acknowledged. We thank anonymous reviewers for valuable comments and critical reading.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/5/16
Y1 - 2019/5/16
N2 - Designed inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase from previous experiments show high binding affinities. In this work, the binding affinities of these designed inhibitors are determined via free energy simulations. The calculated values agree well with the corresponding experimental results. Several structurally different inhibitors share extremely similar binding affinities. Detailed interaction analysis including the hydrogen bond profiles and the interaction energies between the ligand and its surroundings shows large enthalpy changes upon mutation from one ligand to another, while the binding affinities remain unchanged. This finding indicates the existence of entropy-enthalpy compensation.
AB - Designed inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase from previous experiments show high binding affinities. In this work, the binding affinities of these designed inhibitors are determined via free energy simulations. The calculated values agree well with the corresponding experimental results. Several structurally different inhibitors share extremely similar binding affinities. Detailed interaction analysis including the hydrogen bond profiles and the interaction energies between the ligand and its surroundings shows large enthalpy changes upon mutation from one ligand to another, while the binding affinities remain unchanged. This finding indicates the existence of entropy-enthalpy compensation.
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U2 - 10.1016/j.cplett.2019.03.020
DO - 10.1016/j.cplett.2019.03.020
M3 - Article
AN - SCOPUS:85062893618
VL - 723
SP - 1
EP - 10
JO - Chemical Physics Letters
JF - Chemical Physics Letters
SN - 0009-2614
ER -