2 research outputs found
The Role of Conformational Changes in Molecular Recognition
Conformational
changes of molecules are crucial elements in many
biochemical processes, and also in molecular recognition. Here, we
present a novel exact mathematical equation for the binding free energy
of a receptor–ligand pair. It shows that the energetic contribution
due to conformational changes upon molecular recognition is defined
by the so-called Kullback–Leibler (KL) divergence between the
probability distributions of the conformational ensemble of the biomolecule
in the bound and free states. We show that conformational changes
always contribute positively to the change in free energy and therefore
disfavor the association process. Using the example of ligands binding
to a flexible cavity of T4 lysozyme, we illustrate that, due to enthalpy–entropy
compensation, the conformational entropy is a misleading quantity
for assessing the conformational contribution to the binding free
energy, in contrast to the KL divergence, which is the correct quantity
to use in this context
How Molecular Conformational Changes Affect Changes in Free Energy
A simple quantitative relationship
between the molecular conformational
changes and the corresponding changes in the free energy is presented.
The change in free energy is the sum of that part of the enthalpic
change that is due to the externally applied work (perturbation) and
of that part of the entropic change, termed dissipative entropy, that
is related to the conformational changes. The dissipative entropy
is equivalent to the relative entropy, a concept from information
theory, between the distributions of the conformations in the initial
and the final states. The remaining change in entropy (nondissipative)
cancels exactly with the remaining enthalpic change. The calculation
of the dissipative entropy is demonstrated to pose the main difficulty
in free energy computation. The straightforward decomposition of the
dissipative entropy into contributions from different parts of the
system promises to improve the understanding of the role of conformational
changes in biochemical reactions