Searching for a Reliable Density Functional for Molecule–Environment Interactions, Found B97M-V/def2-mTZVP

In
the present study, we have examined density functional theory
methods for the calculation of the interaction energy between a small
molecule and its environment. For simple systems such as a neutral
solute in a neutral solvent, good accuracy can be attained using low-cost
“3c” methods, in particular r2SCAN-3c. When
part(s) of the system is charged, the accurate computation of the
interactions is more challenging. In these cases, we find the B97M-V/def2-mTZVP
method to agree well with reference values; it also shows good accuracy
for the more straightforward neutral systems. Thus, B97M-V/def2-mTZVP
provides a means for accurate and low-cost computation of interaction
energies, notably the binding between a substrate or a drug molecule
and an enzyme, which may facilitate rational drug design.