Docking studies and molecular dynamics simulation of triazole benzene sulfonamide derivatives with human carbonic anhydrase IX inhibition activity
Pushparathinam Gopinath, M. K. Kathiravan
Abstract
) and interactions with Gln92, Thr200, Asn66 and His68. Desmond's molecular dynamics simulations studies for 100 ns of compound 27 compared to reference SLC0111 provided useful structural insights of human carbonic anhydrase IX inhibition. Compound 27 with new chemical structure displayed both hydrophobic and hydrophilic stable interactions in the active site. RMSD, RMSF, RoG, H-bond and SASA analysis confirmed the stable binding of compound 27 with 5FL4 structure. In addition, MM-PBSA and MM-GBSA also affirm the docking results. We propose the designed compound 27 (predicted Ki = ∼0.07 nM) as the best theoretical lead which may further be experimentally studied for selective inhibition.
Topics & Concepts
ChemistryDocking (animal)Molecular dynamicsAutoDockCarbonic anhydraseQuantitative structure–activity relationshipStereochemistrySulfonamideDimerCarbonic anhydrase IIMoleculeEnzymeCombinatorial chemistryComputational chemistryBiochemistryOrganic chemistryNursingIn silicoMedicineGeneEnzyme function and inhibitionSynthesis and Catalytic ReactionsChemical Reaction Mechanisms