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Chitosan is a functional polymer with diverse applications in biomedicine, agriculture, water treatment, and beyond. Via derivatization of pristine chitosan, its functionality can be tailored to desired applications, e.g. immobilization of biomolecules. Here, we performed molecular dynamics simulations of three aminated chitosan polymers, where one, two, and three long-distanced side chains have been incorporated. These polymers have been previously synthesized and their properties were investigated experimentally, however, the observed dependencies could not be fully explained on the molecular level. Here, we develop a computational protocol for the simulation of functionalized chitosan polymers and perform advanced analysis of their conformational states, intramolecular interactions, and water binding. We demonstrate that intra- and intermolecular forces, especially hydrogen bonds induced by polymer side chain modifications, modulate dihedral angle conformational states of the polymer backbone and interactions with water. We explain the role of the chemical composition of the functionalized chitosans in their tendency to collapse and reveal the key role of the protonation of the amino group near the polymer backbone on the reduction of polymer collapse. We demonstrate that specific binding of water molecules, especially the intermediate water, is more pronounced in the polymer exhibiting such an amino group., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Phytochromes are biological photoreceptors found in all kingdoms of life. Numerous physicochemical and spectroscopic studies of phytochromes have been carried out for many decades, both experimentally and computationally, with the main focus on the photoconversion mechanism involving a tetrapyrrole chromophore. In this computational work, we concentrate on the long-scale dynamic motion of the photosensory domain of Deinococcus radiodurans by means of classical all-atom molecular dynamics (MD) simulations. Conventional and accelerated MD methods in combination with two different force fields, CHARMM27 and AMBER ff14SB, are tested in long atomistic simulations to confront the dynamics of monomer and dimer forms. These calculations highlight dissimilar equilibrium conformations in aqueous solutions and, in turn, different large-scale dynamic behaviors of the monomer form vs the dimer form. While the phytochrome in a monomer form tends to close the cavity entailed between the GAF and PHY domains, the opposite trend is predicted for the phytochrome dimer, which opens up as a consequence of the formation of strong salt bridges between the PHY domains of two molecules in water.

Superoxide reductases are non-heme iron enzymes that represent valuable model systems for the reductive detoxification of reactive oxygen species. In the present study, we applied different theoretical methods to study the structural dynamics of a prototypical 2Fe-superoxide reductase and its influence on electron transfer towards the active site. Using normal mode and essential dynamics analyses, we could show that enzymes of this type are capable of well-defined, electrostatically triggered domain movements, which may allow conformational proofreading for cellular redox partners involved in intermolecular electron transfer. Moreover, these global modes of motion were found to enable access to molecular configurations with decreased tunnelling distances between the active site and the enzyme's second iron centre. Using all-atom classical molecular dynamics simulations and the tunnelling pathway model, however, we found that electron transfer between the two metal sites is not accelerated under these conditions. This unexpected finding suggests that the unperturbed enzymatic structure is optimized for intramolecular electron transfer, which provides an indirect indication of the biological relevance of such a mechanism. Consistently, efficient electron transfer was found to depend on a distinct route, which is accessible via the equilibrium geometry and characterized by a quasi conserved tyrosine that could enable multistep-tunnelling (hopping). Besides these explicit findings, the present study demonstrates the importance of considering both global and local protein dynamics, and a generalized approach for the functional analysis of these aspects is provided.

Sulfite oxidase (SO) is an enzyme catalyzing the terminal step of the metabolism of sulfur-containing amino acids that is essential for almost all living organisms. The catalytic activity of SO in vertebrates strongly depends on the efficiency of the intramolecular electron transfer (IET) between the catalytic Moco domain and the cytochrome b5 (cyt b5) domain. The IET process is assumed to be mediated by large domain motions of the cyt b5 domains within the enzyme. Thus, the interaction of SO with charged surfaces may affect the mobility of the cyt b5 domain required for IET and consequently hinder SO activation. In this study, we present a molecular dynamics approach to investigating the ionic strength dependence of the initial surface adsorption of SO in two different conformations-the crystallographic structure and the model structure for an activated SO-onto mixed amino- and hydroxyl-terminated SAMs. The results show for both conformations at low ionic strengths a strong adsorption of the cyt b5 units onto the SAM, which inhibits the domain motion event required for IET. Under higher ion concentrations, however, the interaction with the surface is weakened by the negatively charged ions acting as a buffer and competing in adsorption with the cathodic cyt b5 domains. This competition prevents the immobilization of the cytochrome b5 units onto the surface, allowing the intramolecular domain motions favoring IET. Our predictions support the interpretation of recent experimental spectroelectrochemical studies on SO.

We present a novel approach for determining the strength of the electric field experienced by proteins immobilised on membrane models. It is based on the vibrational Stark effect of a nitrile label introduced at different positions on engineered proteins and monitored by surface enhanced infrared absorption spectroscopy., (This journal is © The Royal Society of Chemistry 2012)

Bone morphogenetic protein-2 (BMP-2) plays a crucial role in osteoblast differentiation and proliferation. Its effective therapeutic use for ectopic bone and cartilage regeneration depends, among other factors, on the interaction with the carrier at the implant site. In this study, we used classical molecular dynamics (MD) and a hybrid approach of steered molecular dynamics (SMD) combined with MD simulations to investigate the initial stages of the adsorption of BMP-2 when approaching two implant surfaces, hydrophobic graphite and hydrophilic titanium dioxide rutile. Surface adsorption was evaluated for six different orientations of the protein, two end-on and four side-on, in explicit water environment. On graphite, we observed a weak but stable adsorption. Depending on the initial orientation, hydrophobic patches as well as flexible loops of the protein were involved in the interaction with graphite. On the contrary, BMP-2 adsorbed only loosely to hydrophilic titanium dioxide. Despite a favorable interaction energy between protein and the TiO(2) surface, the rapid formation of a two-layer water structure prevented the direct interaction between protein and titanium dioxide. The first water adlayer had a strong repulsive effect on the protein, while the second attracted the protein toward the surface. For both surfaces, hydrophobic graphite and hydrophilic titanium dioxide, denaturation of BMP-2 induced by adsorption was not observed on the nanosecond time scale.

The structural stability and conformational flexibility of two phycocyanobilin (PCB) binding bacteriaphytochromes, namely, Cph1 from Synechocystis and the GAF domain of SyB from Synechococcus, were studied using all-atoms molecular dynamics simulations techniques. In order to involve the tetrapyrrole cofactor in the simulation, new empirical force field parameters were developed for PCB which are compatible with the CHARMM22 force field for proteins. Special emphasis was made in understanding the conflicting NMR-based structures recently obtained for the two parent states, Pr and Pfr, of SyB(GAF) regarding the highly distorted cofactor conformation which is in contrast to all crystallographic measurements on other phytochrome species. The 25 ns all-atoms MD simulation of Cph1 in the Pr state and SyB(GAF) in its two parent states supports the picture of a relatively planar conformation of rings A, B, and C and ring D slightly twisted out of the ABC plane, in good agreement with crystallographic and spectroscopic experiments. SyB(GAF) converges to two very similar structures for the Pr state and also for the Pfr state with a ZZZssa conformation in disagreement with the ZZE configuration observed experimentally for other phytochromes. The failure in the prediction of the SyB(GAF) Pfr geometry is a consequence of deformed initial structure. Furthermore, in contrast to the results obtained for the SyB(GAF), the MD simulations showed a very stable Cph1 structure where an important hydrogen bond and water network in the chromophore binding pocket could be identified. We did not find evidence for structural heterogeneity either for Cph1 or SyB(GAF) at least on the nanosecond time scale.