Computational Prediction of Alanine Scanning and Ligand Binding Energetics in G-Protein Coupled Receptors
Figure 1
Structure of the hY1-BIBP3226 complex, ligand analogs and relative binding free energies.
(A) Starting structure for the FEP calculations. The TM helices of hY1 are shown in anti-clockwise order (TM1, dark blue – TM7, red). Residues for which alanine scanning has been done are coloured according the TM helices and BIBP3226 is shown with magenta carbons. (B) Structure of BIBP3226 and seven analogs [17], [18], where the ligands differ in the R substituent. (C) Calculated and experimental relative binding free energies for BIBP3226 to the thirteen hY1 alanine mutants compared to hY1 wt. Blue bars represent , red bars
from Sautel et al. [15] and green bars
from Sjödin et al.16. For mutants marked with an *,
measured by Sautel et al.15 is larger than 2.3 kcal/mol. (D) Calculated and experimental relative hY1 wt binding free energies for the seven compound analogs compared to BIBP3226. Blue bars represent
and red bars
from Aiglstorfer et al. [17], [18]. Error bars are ±1 s.e.m.