Conformational preferences of 2-[(2-hydroxyethyl)sulfanyl]-4-oxo-4-(2,4-diisopropylphenyl)- butanoic acid phenylamide. The NMR/MD study

Abstract

Title molecule, recently prepared in our laboratory comprises the pharmacophoric pattern of the BH3 domain inhibitors. Such compounds were extensively studied as the antiproliferative agents. In this communication we present its conformational preferences in the solvents of different polarity and HBD/HBA abilities. NOESY spectra of compound were recorded in DMSO-d6 and CDCl3. NOESY cross-peaks and coupling constants were processed by NAMFIS analysis and results compared with the conformational assembly and the free-energy surfaces of compound obtained by molecular dynamics simulations in the corresponding explicit solvents. Adaptive biasing force was used to map free-energy surfaces. Janocchio program was used for the NAMFIS analysis, molecular dynamics simulations (30 ns, each) were performed in NAMD 2.9 using CHARMm22 force field on the multi-node Linux cluster. Conformations of the compound were generated by OMEGA program.