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The ability to redirect electron transport to new reactions in living systems opens possibilities to store energy, generate new products, or probe physiological processes. Recent work by Huang et al. showed that 3D crystals of small tetraheme cytochromes (STC) could transport electrons over nanoscopic to mesoscopic distances by an electron hopping mechanism. Such protein-based structures with multiple localized electron carriers are promising materials for nanowires. A potential barrier to protein nanowire adoption for handling long-range electron transport is that fluctuations at room temperature may distort the nanostructure, hindering efficient electron transport. To study these fluctuations at the nano- and mesoscopic scales, we carry out classical molecular dynamics simulations for a small fragment of a STC nanowire and measure the effective distance distribution between electron carriers. From distance distributions, we develop a graph network representation for electron transport along nanowires with varying dimensions, and through stochastic methods determine the maximum electron flow that can be driven through these STC wires. Longer nanowires were capable of carrying fewer electrons than shorter nanowires with the same diameter, as long electron transfer distances that occasionally arise reduce the efficiency for electron transport. Thicker nanowires permit more alternative transport pathways, increasing electron transport beyond the increase in cross-section. Thus, this model implies that the design of protein-based nanowires that depend on electron hopping between charge carriers must consider control of the inherent protein flexibility, as more flexible protein-protein interfaces impose a limit on the required minimum diameter to carry currents commensurate with conventional electronics.

The thylakoid membrane is in a temperature-sensitive equilibrium that shifts repeatedly during the life cycle in response to ambient temperature or solar irradiance. Plants respond to seasonal temperature by changing their thylakoid lipid composition, while a more rapid mechanism for short-term heat exposure is required. The emission of the small organic molecule isoprene has been postulated as one such possible rapid mechanism. The protective mechanism of isoprene is not known, but some plants emit isoprene during periods of high-temperature stress. In this work, we investigate the dynamics and structure for lipids within a thylakoid membrane at different temperatures and varied isoprene content using classical molecular dynamics simulations. The results are compared with experimental findings from across the literature for temperature-dependent changes in the lipid composition and shape of thylakoids. We find that the surface area, volume, and flexibility of the membrane, as well as the lipid diffusion, increase with temperature, while the membrane thickness decreases. Saturated thylakoid 34:3 glycolipids derived from eukaryotic synthesis pathways exhibit significantly different dynamics than lipids from prokaryotic synthesis paths, which could explain the upregulation of specific lipid synthesis pathways at different temperatures. Increasing isoprene concentration was not observed to have a significant thermoprotective effect on the thylakoid membranes, and that isoprene readily permeated the membrane models tested here.

Secondary plant cell walls are made from three common biopolymers, cellulose, lignin, and hemicellulose, representing a critical feedstock for sustainable biomaterial production. Separating lignocellulosic biomass components for use in tailored sustainable energy and materials applications is challenging, as the biopolymers are in close proximity within the plant secondary cell wall. Organic solvents are used to pretreat recalcitrant biomass and separate the interacting polymers, solubilizing the lignin fraction for lignin-first valorization approaches. However, no single organosolv pretreatment approach has proven superior for heterogeneous biomass samples. Simulation offers a complementary atomic view into interactions between biomass components, resolving mechanistic hypotheses for how biomass composition influences separations processes. Using molecular dynamics simulations, we quantify lignin-cellulose interactions through binding free energies determined from 300 lignin polymer models in nine solvent environments, across four crystalline cellulose faces, with an aggregate simulation time of nearly 154 microseconds. The binding free energy determined from simulation categorizes the solvents. For poor lignin solvents, all lignin polymers bind strongly to cellulose. By contrast, polar protic solvents such as methanol and ethanol favor the unbinding between lignin and cellulose in all conditions, regardless of charge for the lignin monomer tested. Aprotic organic solvents separate lignin from cellulose only for uncharged lignin monomers, with charged lignin monomers associating to cellulose. While polar protic solvents are most effective at breaking apart lignin-cellulose interactions for charged lignin species, solvent dynamics highlight that there is no single optimal solvent to facilitate lignin-cellulose separation, particularly as some solvents demonstrate greater effectiveness for skewed S:G ratios. Instead, the optimal solvent for a given lignin sample will depend on the lignin compound and the net charge for the lignin polymers.

We develop a workflow, implemented as a plugin to the molecular visualization program VMD, that can fix ring penetrations with minimal user input. LongBondEliminator, detects ring piercing artifacts by the long, strained bonds that are the local minimum energy conformation during minimization for some assembled simulation system. The LongBondEliminator tool then automatically treats regions near these long bonds using multiple biases applied through NAMD. By combining biases implemented through the collective variables module, density-based forces, and alchemical techniques in NAMD, LongBondEliminator will iteratively alleviate long bonds found within molecular simulation systems. Through three concrete examples with increasing complexity, a lignin polymer, an viral capsid assembly, and a large, highly glycosylated protein aggrecan, we demonstrate the utility for this method in eliminating ring penetrations from classical MD simulation systems. The tool is available via gitlab as a VMD plugin, and has been developed to be generically useful across a variety of biomolecular simulations.

Description, We observe previously unknown interactions between clinically important adenovirus vector capsids, platelet factor 4, and CAR., Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.