Thermodynamic and transport properties of Belinostat

Abstract

HDACs inhibitors, Belinostat inhibits class I HDACs, class II HDACs and class
IV HDAC proteins activities. Antitumor activity of Belinostat is attributed to epi-
genetic control of gene expression and inhibition of protein repression. In this study,
we have performed molecular dynamics simulation of Belinostat in water at 310 K
temperature to investigate structural, thermodynamic and tranport properties. For
the structural analysis, we have studied the radial distribution function (RDF).
Thermodynamic integration (TI) and free energy perturbation (FEP) based meth-
ods: TI, TI-CUBIC, BAR and MBAR have been used to estimate solvation free
energy. Our calculations show that Coulomb interactions has major contribution to
the solvation free energy of Belinostat in water although both coulomb as well as
vdW interaction contribute. Furthermore, we have estimated the sef-diffusion co-
efficient of both solute and solvent molecules with their binary diffusion coefficient
from the slope of Mean Squared Displacement (MSD) versus time plot using Ein-
stein’s and Darken’s relations respectively. Hydrogen bond and Solvent accessible
surface area (SASA) analyses further support the strong hydration and structural
stability of Belinostat in aqueous enviroment.