Why Solvent Response Contributions to Solvation Free Energies Are Compatible with Ben-Naim's Theorem.

We resolve a seeming paradox arising from a common misinterpretation of Ben-Naim's theorem, which rests on the decomposition of the Hamiltonian of a molecular solute/solvent system into solute-solvent and solvent-solvent interactions. According to this theorem, the solvation entropy can also be decomposed into a solute-solvent term and a remaining solvent-solvent term that is commonly referred to as the solvent reorganization term. Crucially, the latter equals the average solvent-solvent interaction energy such that these two solvent-solvent terms cancel and thus do not change the total solvation free energy.

Tight docking of membranes before fusion represents a metastable state with unique properties.

Membrane fusion is fundamental to biological processes as diverse as membrane trafficking or viral infection. Proteins catalyzing membrane fusion need to overcome energy barriers to induce intermediate steps in which the integrity of bilayers is lost. Here, we investigate the structural features of tightly docked intermediates preceding hemifusion.

Spatially resolved free-energy contributions of native fold and molten-globule-like Crambin.

The folding stability of a protein is governed by the free-energy difference between its folded and unfolded states, which results from a delicate balance of much larger but almost compensating enthalpic and entropic contributions. The balance can therefore easily be shifted by an external disturbance, such as a mutation of a single amino acid or a change of temperature, in which case the protein unfolds. Effects such as cold denaturation, in which a protein unfolds because of cooling, provide evidence that proteins are strongly stabilized by the solvent entropy contribution to the free-energy balance.

Per|Mut: Spatially Resolved Hydration Entropies from Atomistic Simulations.

The hydrophobic effect is essential for many biophysical phenomena and processes. It is governed by a fine-tuned balance between enthalpy and entropy contributions from the hydration shell. Whereas enthalpies can in principle be calculated from an atomistic simulation trajectory, calculating solvation entropies by sampling the extremely large configuration space is challenging and often impossible.

Computing Spatially Resolved Rotational Hydration Entropies from Atomistic Simulations.

For a first-principles understanding of macromolecular processes, a quantitative understanding of the underlying free energy landscape and in particular its entropy contribution is crucial. The stability of biomolecules, such as proteins, is governed by the hydrophobic effect, which arises from competing enthalpic and entropic contributions to the free energy of the solvent shell. While the statistical mechanics of liquids, as well as molecular dynamics simulations, have provided much insight, solvation shell entropies remain notoriously difficult to calculate, especially when spatial resolution is required.

In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways.

The ryanodine receptor 1 is a large calcium ion channel found in mammalian skeletal muscle. The ion channel gained a lot of attention recently, after multiple independent authors published near-atomic cryo electron microscopy data. Taking advantage of the unprecedented quality of structural data, we performed molecular dynamics simulations on the entire ion channel as well as on a reduced model.

In Silico Measurements of Twist and Bend Moduli for β-Solenoid Protein Self-Assembly Units.

We compute potentials of mean force for bend and twist deformations via force pulling and umbrella sampling experiments for four β-solenoid proteins (BSPs) that show promise in nanotechnology applications. In all cases, we find quasi-Hooke's law behavior until the point of rupture. Bending moduli show modest anisotropy for two-sided and three-sided BSPs, and little anisotropy for a four-sided BSP.