The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction

Yuchen Li, Yalong Cong, Guoqiang Feng, Susu Zhong, John Z.H. Zhang, Huiyong Sun, Lili Duan

Research output: Contribution to journalArticlepeer-review


At present, the calculated binding free energy obtained using the molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area (MM/PB(GB)SA) method is overestimated due to the lack of knowledge of suitable interior dielectric constants in the simulation on the interaction of Human Immunodeficiency Virus (HIV-1) protease systems with inhibitors. Therefore, the impact of different values of the interior dielectric constant and the entropic contribution when using the MM/PB(GB)SA method to calculate the binding free energy was systemically evaluated. Our results show that the use of higher interior dielectric constants (1.4-2.0) can clearly improve the predictive accuracy of the MM/PBSA and MM/GBSA methods, and computational errors are significantly reduced by including the effects of electronic polarization and using a new highly efficient interaction entropy (IE) method to calculate the entropic contribution. The suitable range for the interior dielectric constant is 1.4-1.6 for the MM/PBSA method; within this range, the correlation coefficient fluctuates around 0.84, and the mean absolute error fluctuates around 2 kcal/mol. Similarly, an interior dielectric constant of 1.8-2.0 produces a correlation coefficient of approximately 0.76 when using the MM/GBSA method. In addition, the entropic contribution of each individual residue was further calculated using the IE method to predict hot-spot residues, and the detailed binding mechanisms underlying the interactions of the HIV-1 protease, its inhibitors, and bridging water molecules were investigated. In this study, the use of a higher interior dielectric constant and the IE method can improve the calculation accuracy of the HIV-1 system.

Original languageEnglish (US)
Article number064101
JournalStructural Dynamics
Issue number6
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Radiation
  • Instrumentation
  • Condensed Matter Physics
  • Spectroscopy


Dive into the research topics of 'The impact of interior dielectric constant and entropic change on HIV-1 complex binding free energy prediction'. Together they form a unique fingerprint.

Cite this