Calculated and experimental mutational energies (kcal/mol) of ImI mutants.

aMinimization based approach (MBA), which uses either a distance-dependent dielectric constant minimization (DDDCM) or an explicit water minimization (EWM). The standard deviations of the mutational energies were computed using 15 frames.bMolecular dynamics simulation based approach (MDBA). Five different strategies, noted (i) to (v), were used to refine the conformation of the structural model. (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; (v) all residues were restrained to their position. The standard deviations of the mutational energies were computed using 50 frames.cExperimental mutational energies (EXP). The values were derived from experimental Kd values [26]–[28] using the equation ΔΔGbinding = EXP = −RT ln[Kd (mutant)/Kd (wild-type)] at 298 K.dMutational energy computed using molecular mechanics generalized Born (GB) surface area (MM-GB/SA) at 298 K.eMutational energy computed using molecular mechanics Poisson-Boltzmann (PB) surface area (MM-PB/SA) at 298 K.