Driving Structural Transitions in Molecular Simulations Using the Nonequilibrium Candidate Monte Carlo.

Hybrid simulation procedures which combine molecular dynamics with Monte Carlo are attracting increasing attention as tools for improving the sampling efficiency in molecular simulations. In particular, encouraging results have been reported for nonequilibrium candidate protocols, in which a Monte Carlo move is applied gradually, and interleaved with a process that equilibrates the remaining degrees of freedom. Although initial studies have uncovered a substantial potential of the method, its practical applicability for sampling structural transitions in macromolecules remains incompletely understood.

Dimerization of Terminal Domains in Spiders Silk Proteins Is Controlled by Electrostatic Anisotropy and Modulated by Hydrophobic Patches.

The well-tuned spinning technology from spiders has attracted many researchers with the promise of producing high-performance, biocompatible, and yet biodegradable fibers. So far, the intricate chemistry and rheology of spinning have eluded us. A breakthrough was achieved recently, when the 3D structures of the N and C terminal domains of spider dragline silk were resolved and their pH-induced dimerization was revealed.

Role of histidine for charge regulation of unstructured peptides at interfaces and in bulk.

Histidine-rich, unstructured peptides adsorb to charged interfaces such as mineral surfaces and microbial cell membranes. At a molecular level, we investigate the adsorption mechanism as a function of pH, salt, and multivalent ions showing that (1) proton charge fluctuations are-in contrast to the majority of proteins-optimal at neutral pH, promoting electrostatic interactions with anionic surfaces through charge regulation and (2) specific zinc(II)-histidine binding competes with protons and ensures an unusually constant charge distribution over a broad pH interval. In turn, this further enhances surface adsorption.

High expression of midkine in the airways of patients with cystic fibrosis.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in impaired host defense during cystic fibrosis (CF), where Pseudomonas aeruginosa becomes a key pathogen. We investigated the expression pattern of the antibacterial growth factor midkine (MK) in CF and the possible interference with its activity by the altered airway microenvironment. High MK expression was found in CF lung tissue compared with control samples, involving epithelia of the large and small airways, alveoli, and cells of the submucosa (i.

Solution electrostatics beyond pH: a coarse grained approach to ion specific interactions between macromolecules.

Oblivious to ion specificity, pH has been a key parameter for macromolecular solutions for little more than a century. We here widen the concept by describing the ionization of macromolecules not only via pH, but also pX where X are other binding species. Using binding constants, measured by NMR, of chloride and thiocyanate to amino acid motifs on y-crystallin, we calculate i) titration curves as a function of pH and pX and ii) estimate second virial coefficients using both approximate theory and computer simulations.

Anisotropic Interactions in Protein Mixtures: Self Assembly and Phase Behavior in Aqueous Solution.

Recent experimental studies show that oppositely charged proteins can self-assemble to form seemingly stable microspheres in aqueous salt solutions. We here use parallel tempering Monte Carlo simulations to study protein phase separation of lysozyme/α-lactalbumin mixtures and show that anisotropic electrostatic interactions are important for driving protein self-assembly. In both dilute and concentrated protein phases, the proteins strongly align according to their charge distribution.