Computational Analysis of Residue-Specific Binding Free Energies of Androgen Receptor to Ligands

Guangfeng Shao, Jingxiao Bao, Xiaolin Pan, Xiao He, Yifei Qi, John Z.H. Zhang

Research output: Contribution to journalArticlepeer-review


Androgen receptor (AR) is an important therapeutic target for the treatment of diseases such as prostate cancer, hypogonadism, muscle wasting, etc. In this study, the complex structures of the AR ligand-binding domain (LBD) with fifteen ligands were analyzed by molecular dynamics simulations combined with the alanine-scanning-interaction-entropy method (ASIE). The quantitative free energy contributions of the pocket residues were obtained and hotspot residues are quantitatively identified. Our calculation shows that that these hotspot residues are predominantly hydrophobic and their interactions with binding ligands are mainly van der Waals interactions. The total binding free energies obtained by summing over binding contributions by individual residues are in good correlation with the experimental binding data. The current quantitative analysis of binding mechanism of AR to ligands provides important insight on the design of future inhibitors.

Original languageEnglish (US)
Article number646524
JournalFrontiers in Molecular Biosciences
StatePublished - Mar 12 2021


  • GBSA
  • MD simulation
  • alanine scanning
  • androgen receptor
  • hotspot
  • interaction entropy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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