A DFT approach to discriminate the antagonist and partial agonist activity of ligands binding to the NMDA receptor

Abstract

Index S2 2D molecular structures S3 Global descriptors S7 Local descriptors S11 Comparison of global molecular descriptors S17 Correlation plot for chemical hardness S18 Comparison of local molecular descriptors S19 Efficacy of partial agonists S22 Cartesian coordinates of partial agonists (zwitterion)-B3LYP S23 Cartesian coordinates of partial agonists (zwitterion)-M06-2X S42 Cartesian coordinates of partial agonists (neutral)-B3LYP S48 Cartesian coordinates of antagonists-B3LYP S67 Cartesian coordinates of antagonists-M06-2X S91 Additional molecular structures-B3LYP S99 S3 2D molecular structures Table S1 Two-dimensional representations of selected antagonist molecules (*Yosa et al.[1]; **Di Fabio et al.[2]) ID 2D STRUCTURE pKi ID 2D STRUCTURE pKi 189* Table S11 Mulliken charge on the amide oxygen and nitrogen atom for the selected antagonists (M06-2X/6-311G**). ligand qO qN 189 -0.450 -0.564 192 -0.451 -0.556 210 -0.442 -0.560 213 -0.442 -0.561 217 -0.443 -0.560 29 -0.455 -0.564 41 -0.443 -0.575 24 -0.461 -0.560 38 -0.444 -0.544 44 -0.457 -0.563 Table S12 Mulliken charge on the amide oxygen and nitrogen atom for the selected partial agonists in their zwitterionic form (M06-2X/6-311G**). ligand qO qN Z9 -0.521 -0.474 Z15 -0.511 -0.481 Z19 -0.498 -0.467 Z22 -0.503 -0.468 Z26 -0.508 -0.472 Z29 -0.490 -0.466 Z35 -0.505 -0.468 Z39 -0.506 -0.468 Z46 -0.492 -0.460 Z51 -0.500 -0.470 S15 Table S13 Amide's carbonyl stretching frequency (cm -1 ), and isotropic magnetic chemical shielding constants for the amide's oxygen and nitrogen atom (ppm) for the antagonists (B3LYP/6-311G**).

Stability, Bioavailability, and Structure–Activity Relationship of Casein-Derived Peptide YPVEPF with a Sleep-Enhancing Effect

“…Many scholars proposed that the activity of agonists for the GABA A receptor at BZD sites was closely related to the electron transfer in the frontier molecular orbital, and the electron transfer participated in BZD activity by the mode of action in cell signaling. , To further explain the different activities of YPVEPF and its metabolites, the electronic characteristics were calculated by a quantum mechanical (QM) assay. QM property fields were commonly used to understand novel structure–activity relationship features in many studies. − As shown in Figure , the Mulliken electronegativity χ values of YPVEPF and YPVEP (80.22 and 78.45 kcal/mol, respectively) were lower than those of PVEPF and PVEP (85.51 and 84.29 kcal/mol, respectively), indicating that the peptides YPVEP and YPVEPF had relatively higher electron-donating ability compared with PVEPF and PVEP. In addition, the results showed that the HOMO and LUMO states for the four peptides were all considerably set apart and localized on the right and left half of the peptides.…”