He thereby introduced the concept of statistical disorder and probability distributions into a new field of thermodynamics, called statistical mechanics, and found the link between the microscopic interactions, which fluctuate about an average configuration, to the macroscopically observable behavior, in form of a simple logarithmic law, with a proportionality constant, the Boltzmann constant, that has become one of the defining universal constants for the modern International System of Units (SI). Entropy is central to the second law of thermodynamics, which states that the entropy of isolated systems left to spontaneous evolution cannot decrease with time, as they always arrive at a state of thermodynamic equilibrium, where the entropy is highest.Īustrian physicist Ludwig Boltzmann explained entropy as the measure of the number of possible microscopic arrangements or states of individual atoms and molecules of a system that comply with the macroscopic condition of the system. Ī consequence of entropy is that certain processes are irreversible or impossible, aside from the requirement of not violating the conservation of energy, the latter being expressed in the first law of thermodynamics. Referring to microscopic constitution and structure, in 1862, Clausius interpreted the concept as meaning disgregation. He initially described it as transformation-content, in German Verwandlungsinhalt, and later coined the term entropy from a Greek word for transformation. In 1865, German physicist Rudolf Clausius, one of the leading founders of the field of thermodynamics, defined it as the quotient of an infinitesimal amount of heat to the instantaneous temperature. The thermodynamic concept was referred to by Scottish scientist and engineer Macquorn Rankine in 1850 with the names thermodynamic function and heat-potential. It has found far-ranging applications in chemistry and physics, in biological systems and their relation to life, in cosmology, economics, sociology, weather science, climate change, and information systems including the transmission of information in telecommunication. The term and the concept are used in diverse fields, from classical thermodynamics, where it was first recognized, to the microscopic description of nature in statistical physics, and to the principles of information theory. Our results support a model whereby the specific surface properties of JNK1 and p38α dictate the bound conformation of MKK4 and that enthalpy–entropy compensation plays a major role in maintaining comparable binding affinities for MKK4 towards the two kinases.Entropy is a scientific concept as well as a measurable physical property that is most commonly associated with a state of disorder, randomness, or uncertainty. Here we show, using a combination of nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC), that the promiscuous interaction of the intrinsically disordered regulatory domain of the mitogen-activated protein kinase kinase MKK4 with p38α and JNK1 is facilitated by folding-upon-binding into two different conformations, despite the high sequence conservation and structural homology between p38α and JNK1. Intrinsically disordered proteins (IDPs) can engage in promiscuous interactions with their protein targets however, it is not clear how this feature is encoded in the primary sequence of the IDPs and to what extent the surface properties and the shape of the binding cavity dictate the binding mode and the final bound conformation.
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