posted on 2021-03-15, 16:36authored byAnkita Katiyar, Ward H. Thompson
Understanding
the structure of proteins is key to unraveling their
function in biological processes. Thus, significant attention has
been paid to the calculation of conformational free energies. In this
paper, we demonstrate a simple extension of fluctuation theory that
permits the calculation of the temperature derivative of the conformational
free energy, and hence the internal energy and entropy, from single-temperature
simulations. The method further enables the decomposition into the
contribution of different interactions present in the system to the
internal energy surface. We illustrate the method for the canonical
test system of alanine dipeptide in aqueous solution, for which we
examine the free energy as a function of two dihedral angles. This
system, like many, is most effectively treated using accelerated sampling
methods and we show how the present approach is compatible with an
important class of these, those that introduce a bias potential, by
implementing it within metadynamics.