Abstract: The rate constant of an enzyme-catalysed reaction is one of the
major target properties to understand protein function. Atomic-detail computer
simulations can in principle be used to estimate rate constants from the energy
profile along the reaction coordinate. For such simulations, molecular
mechanics is combined with a quantum description of the reaction process. In
molecular mechanics calculations, the electrostatic field is represented by the
Coulomb potential of partial atomic charges which have been parametrised for
small building blocks in vacuum and transferred to the macromolecule. In
aqueous solution, however, the electrostatic interactions are affected by the
solvent polarization. While this can be described by numerically solving the
Poisson–Boltzmann equation, it is computationally expensive. A simple
approximation to this is to optimally reproduce the electrostatic potential in
solution by reparametrising the partial atomic charges in such a way that a
simple Coulomb potential can still be used. Such a procedure would allow to
perform fast calculations of reaction processes in proteins while accounting
for the solvent screening effect. Here, this method is tested on myosin, a
motor protein that is both an enzyme and exists in very different
conformations.
