title: Molecular dynamics simulations and MM/GBSA methods to investigate binding mechanisms of aminomethylpyrimidine inhibitors with DPP-IV.
abstract: The aminomethylpyrimidines were investigated as a novel class of DPP-IV inhibitors. In this Letter, the binding mechanisms of how slight change of substitution or position influences the binding affinity of five representative analogs was investigated by molecular dynamics simulation, free energy calculations and energy decomposition analysis. The conserved hydrogen bonds with Glu205 and Glu206 slightly favor the inhibitor binding; the van der Waals interactions, especially the two key contacts with Tyr547 and Tyr666, dominate in the binding free energy and play a crucial role on distinguishing the high active inhibitors from the low ones.
authors: College of Chemistry and Chemical Engineering, Graduate University of the Chinese Academy of Sciences, Beijing 100049, PR China.
authors: Liang
authors: L
authors: Desheng
authors: Gao
authors: G
authors: Jian
authors: Cheng
authors: C
authors: Yuanhua
authors: Cui
authors: C
authors: Wei
authors: Zhang
authors: Z
authors: Huai
authors: Ji
authors: J
authors: Mingjuan
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; C495751:aminomethylpyrimidine; D018819:Dipeptidyl Peptidase 4