Molecular dynamics simulation and free energy calculation studies of Coagulin L as dipeptidyl peptidase-4 inhibitor

Plant derived product can be used as other alternatives to currently used drugs for controlling chronic diseases like Diabetes mellitus. The potential of Coagulin L (a constituent of Withania coagulans) as dipeptidyl peptidase-4 (DPP-4) inhibitor was evaluated by molecular modelling study. It was observed that amino acid residues such as Glu205, Glu206, Tyr 547, His 740, and Try662 interacts with Coagulin L and Saxagliptin (a known DPP-4 inhibitor). Other nonbonded interactions of Coagulin L and Saxagliptin with DPP-4 binding residues were also found similar. The docking energy of Coagulin L was found to be -7.69 Kcal/mol whereas -8.44 kcal/mol was recorded for Saxagliptin. MD simulation study revealed stable binding throughout 100 ns simulation. RMSD plot of the complex was stabilized in 43 ns and remained stable during entire simulation(100 ns). RMSF plot of DPP-4 Coagulin L interaction showed major fluctuations at residue 246 and 766, however, Arg 125, Glu 205, Ser 209 and His 740 showed no major perturbations. Principal Component Analysis showed that important dynamics of the protein remain unchanged during entire simulation since the non-polar, van der waals, ionic interaction and solvation energy, altogether play important role in the complex stability. The molecular modelling study of DPP-4 with Coagulin L was an effort to establish correlation with traditional practices of Withania coagulans as antidiabetic agent in Indian subcontinent.Communicated by Ramaswamy H. Sarma.