We start with a clear distinction between Shannon’s Measure of Information (SMI) and the Thermodynamic Entropy. The first is defined on any probability distribution; and therefore it is a very general concept. On the other hand Entropy is defined on a very special set of distributions. Next we show that the Shannon Measure of Information (SMI) provides a solid and quantitative basis for the interpretation of the thermodynamic entropy. The entropy measures the uncertainty in the distribution of the locations and momenta of all the particles; as well as two corrections due to the uncertainty principle and the indistinguishability of the particles. Finally we show that the H-function as defined by Boltzmann is an SMI but not entropy. Therefore; much of what has been written on the H-theorem is irrelevant to entropy and the Second Law of Thermodynamics.

Attempts to answer the Levinthal question "How proteins fold to give such a unique structure" are discussed. In the first part of this article, we focus on a few reasons as to why the solution to the protein-folding problem (PFP) has been elusive for a very long time. One is a result of the misinterpretation of Anfinsen's Thermodynamic hypothesis which led to the conclusion that the native structure of a protein must be at a global minimum of the Gibbs energy. The second is the result of the adherence to the hydrophobic paradigm, and at the same time ignoring a whole repertoire of hydrophilic effects. It is argued that switching from a target-based to a caused-based approach, and adopting the hydrophilic paradigm leads straightforwardly to a simple answer to Levinthal's question, as well as to a solution of the PFP.

We analyze all the contributions to the standard free energy of association between two proteins. We find that the solvent-induced interactions between two (or more) hydrophilic groups can turn a highly unfavorable process of association into a highly favorable one. We therefore argue that in contrast to the generally accepted view, it is the hydrophilic rather than the hydrophobic effect that is dominant in biochemical processes such as protein-protein association, protein folding, and protein binding to DNA.

This article is about the profound misuses, misunderstanding, misinterpretations and misapplications of entropy, the Second Law of Thermodynamics and Information Theory. It is the story of the “Greatest Blunder Ever in the History of Science”. It is not about a single blunder admitted by a single person (e.g., Albert Einstein allegedly said in connection with the cosmological constant, that this was his greatest blunder), but rather a blunder of gargantuan proportions whose claws have permeated all branches of science; from thermodynamics, cosmology, biology, psychology, sociology and much more.

The Kirkwood–Buff integrals (KBIs) for one-component systems are calculated from either the pair correlation functions or from experimental macroscopic quantities. As in the case of mixtures, the KBIs provide important information on the local densities around a molecule. In the low density limit (ρ→0) one can extract from the KBI some information on the strength of the intermolecular forces. No such information may be extracted from the KBIs at higher densities. We used experimental data on densities and isothermal compressibilities to calculate the KBIs for various liquids ranging from inert molecules, to hydrocarbons, alcohols, and liquid water.