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

Zhaoxi Sun, Xiaohui Wang, John Z.H. Zhang

Research output: Contribution to journalArticle


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
StatePublished - May 16 2019


ASJC Scopus subject areas

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

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