Non-covalent molecular association underlies a diverse set of biologically and technologically relevant phenomena, including the action of drugs on their biomolecular targets and self- and supra-molecular assembly processes. Computer models employed to model binding frequently use interaction potentials with atomistic detail while neglecting the thermal molecular motions of the binding species....

The four tissue inhibitors of metalloproteinases (TIMPs) are potent inhibitors of the many matrixins (MMPs), except that TIMP1 weakly inhibits some MMPs, including MMP14. The broad-spectrum inhibition of MMPs by TIMPs and their N-domains (NTIMPs) is consistent with the previous isothermal titration calorimetric finding that their interactions are entropy-driven but differ in contributions from ...

Introduction and Aims: Alzheimer’s disease is the most prevalent neurodegenerative disorder and a type of dementia. 80% of dementia in older adults is because of Alzheimer’s disease. According to multiple research articles, Alzheimer's has several changes in EEG signals such as slowing of rhythms, reduction in complexity and reduction in functional associations, and disordered functional commun...

Entropic effects have often been invoked to explain the extraordinary catalytic power of enzymes. In particular, the hypothesis that enzymes can use part of the substrate-binding free energy to reduce the entropic penalty associated with the subsequent chemical transformation has been very influential. The enzymatic reaction of cytidine deaminase appears to be a distinct example. Here, substrat...

We report a new free energy decomposition that includes structure-derived atomic contact energies for the desolvation component, and show that it applies equally well to the analysis of single-domain protein folding and to the binding of flexible peptides to proteins. Specifically, we selected the 17 single-domain proteins for which the three-dimensional structures and thermodynamic unfolding f...

The second generation Mining Minima method yields binding affinities accurate to within 0.8 kcal/mol for the associations of alpha-, beta-, and gamma-cyclodextrin with benzene, resorcinol, flurbiprofen, naproxen, and nabumetone. These calculations require hours to a day on a commodity computer. The calculations also indicate that the changes in configurational entropy upon binding oppose associ...

The importance of dynamic effects of allosteric drug design are now being recognized. Allosteric communication derives from the propagation of effects between distant points in a protein and is closely related to transfer of entropy between these points. In this communication, two methods of evaluating entropy transfer between residues are presented.The first method isbased on extensive molecul...

For several GPCRs, discrimination between agonism and antagonism is possible on the basis of thermodynamics parameters, such as binding enthalpy and entropy. In this study, we analyze whether agonists and antagonists can also be discriminated thermodynamically at the histamine H(1) receptor (H(1)R). Because previous studies revealed species differences in pharmacology between human H(1)R (hH(1)...

Time and temperature dependence of the binding of 3H-dihydroalprenolol (3H-DHA) to beta-adrenergic receptors in rat cerebral cortex is described. The kinetic data obtained suggest that 3H-DHA binding proceeds through a two-step reaction scheme consisting of a bimolecular association step followed by an unimolecular internal conversion of the radioligand receptor complex (isomerisation). Equilib...

the time evaluation of quantum entropy in a four-level double- type atomic system is theoretically investigated. quantum entanglement of the atom and its spontaneous emission fields is then discussed via quantum entropy. it is found that the degree of entanglement can be increased by the quantum interference induced by spontaneous emission. the phase dependence of the atom-field entanglement is...