Blockade of Neuronal α7-nAChR by α-Conotoxin ImI Explained by Computational Scanning and Energy Calculations
Figure 8
Correlation between experimentally derived and calculated mutational energies of ImI mutants in the molecular dynamics based approach MDBA.
Mutational energies were computed by using either molecular mechanics generalized Born (GB) surface area (MM-GB/SA) or molecular mechanics Poisson-Boltzmann (PB) surface area (MM-PB/SA) approaches at 298 K. In the MDBA five alternative position restraint strategies were employed: (i) all receptor atoms >6 Å from the conotoxin were restrained to their position; (ii) all receptor atoms >4.5 Å from the conotoxin were restrained to their position; (iii) all the atoms located >6 Å from the mutated residue were restrained to their position; (iv) all the atoms from the receptor were restrained to their position, and all the atoms from the conotoxin mutants were free to move; and (v) all residues were restrained to their position. Experimental mutational energies (ΔΔG Exp) were derived using the corresponding Kd values of ImI wild-type/α7-nAChR and ImI mutants/α7-nAChR [26]–[28].