HDACs inhibitors, Belinostat inhibits class I HDACs, class II HDACs and classIV 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 Ktemperature to investigate structural, thermodynamic and tranport properties. Forthe 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 freeenergy. Our calculations show that Coulomb interactions has major contribution tothe solvation free energy of Belinostat in water although both coulomb as well asvdW interaction contribute. Furthermore, we have estimated the sef-diffusion co-efficient of both solute and solvent molecules with their binary diffusion coefficientfrom the slope of Mean Squared Displacement (MSD) versus time plot using Ein-stein’s and Darken’s relations respectively. Hydrogen bond and Solvent accessiblesurface area (SASA) analyses further support the strong hydration and structuralstability of Belinostat in aqueous enviroment.
Gautam et al. (Mon,) studied this question.