Summary
Conformational entropy can increase or decrease following ligand binding (1,2). Variation in conformational entropy changes are due to whether the enthalpy effect of small molecule binding is enough to counteract the loss of entropy.
Details
The classical view of small molecule binding is that it sharpens the energy minima of enzymes. (2) provide several examples of this, including triosephosphate isomerase, orotidine 5-monophosphate decarboxylase, glycerol-3-phosphate dehydrogenase, and beta-phosphoglucomutase. However, there are examples of the opposite happening. In (cAMP-dependent protein kinase A), greater dynamics are observed with (NMR) following binding of ATP (3).
1.
Wankowicz SA, Fraser JS. Advances in uncovering the mechanisms of macromolecular conformational entropy. Nature Chemical Biology. 2025;21(5):623–34. Available from: https://doi.org/10.1038/s41589-025-01879-3
2.
Corbella M, Pinto GP, Kamerlin SCL. Loop dynamics and the evolution of enzyme activity. Nature Reviews Chemistry. 2023;7(8):536–47. Available from: https://doi.org/10.1038/s41570-023-00495-w
3.
Wang Y, V.S. M, Kim J, Li G, Ahuja LG, Aoto P, et al. Globally correlated conformational entropy underlies positive and negative cooperativity in a kinase’s enzymatic cycle. Nature Communications. 2019;10(1). Available from: https://doi.org/10.1038/s41467-019-08655-7