Determination of binding affinities of 3-Hydroxy-3-Methylglutaryl Coenzyme A reductase inhibitors from free energy calculation

Zhaoxi Sun, Xiaohui Wang, John Zhang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalChemical Physics Letters
Volume723
DOIs
StatePublished - May 16 2019

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coenzymes
inhibitors
Free energy
affinity
Enthalpy
Oxidoreductases
free energy
Ligands
Hydrogen bonds
Entropy
enthalpy
ligands
mutations
Experiments
interactions
entropy
hydrogen bonds
3-hydroxy-3-methylglutaryl-coenzyme A
profiles
simulation

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

Cite this

Determination of binding affinities of 3-Hydroxy-3-Methylglutaryl Coenzyme A reductase inhibitors from free energy calculation. / Sun, Zhaoxi; Wang, Xiaohui; Zhang, John.

In: Chemical Physics Letters, Vol. 723, 16.05.2019, p. 1-10.

Research output: Contribution to journalArticle

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