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The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Moreover, heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. In this paper, we have shown that the SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. These interactions suggests that the heparin-binding site on the S1 protein might assist the binding of amyloid proteins to the viral surface and thus could initiate aggregation of these proteins and finally leads to neurodegeneration in brain. The results will help us to prevent future outcomes of neurodegeneration by targeting this binding and aggregation process. • SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. • Heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. • SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. • Heparin-binding site on the S1 might assist the binding of amyloid proteins to the viral surface and thus could leads to neurodegeneration in brain. [ABSTRACT FROM AUTHOR]

Many proteins exhibit strong binding affinities to surfaces, with binding energies much greater than thermal fluctuations. When modelling these protein-surface systems with classical molecular dynamics (MD) simulations, the large forces that exist at the protein/surface interface generally confine the system to a single free energy minimum. Exploring the full conformational space of the protein, especially finding other stable structures, becomes prohibitively expensive. Coupling MD simulations with metadynamics (enhanced sampling) has fast become a common method for sampling the adsorption of such proteins. In this paper, we compare three different flavors of metadynamics, specifically well-tempered, parallel-bias, and parallel-tempering in the well-tempered ensemble, to exhaustively sample the conformational surface-binding landscape of model peptide GGKGG. We investigate the effect of mobile ions and ion charge, as well as the choice of collective variable (CV), on the binding free energy of the peptide. We make the case for explicitly biasing ions to sample the true binding free energy of biomolecules when the ion concentration is high and the binding free energies of the solute and ions are similar. We also make the case for choosing CVs that apply bias to all atoms of the solute to speed up calculations and obtain the maximum possible amount of information about the system. [ABSTRACT FROM AUTHOR]

The effect of N 2 H 4 (hydrazine) on AnAOB (anaerobic ammonia oxidizing bacteria) metabolic pattern is unknown. Therefore, the main purpose of this paper was to explore the effects of exogenous N 2 H 4 on the SAA (specific anammox activity), characteristics and metabolic pathway of AnAOB. The results showed that low N 2 H 4 concentration (1–5 mg/L) continuous dosing can promote SAA. The promoting effect was found to be more obvious within the dosage of 3–5 mg/L N 2 H 4. It was also indicated that high N 2 H 4 concentration dosing (5–10 mg/L) can trigger the self-protection mechanism of AnAOB granular sludge by secreting a large amount of B-PN (binding polymeric protein). Intermittent addition of N 2 H 4 at low concentration is conducive to the long-term stable operation of anammox process. Exogenous N 2 H 4 can be directly oxidized by AnAOB to promote the consumption of NO 2 −-N and NH 4 +-N. In addition, excess electrons can also drive the process of NO 3 −-N reduction and NO 2 −-N disproportionation. Theoretically, these reaction processes need two and ten extra electrons respectively, which is not easy to occur compared with the anammox process. [Display omitted] • High N 2 H 4 concentration triggered excessive secretion of binding polymeric protein. • The oxidation of N 2 H 4 enhanced the nitrite reduction and anammox process. • N 2 H 4 drive the nitrate reduction and nitrite disproportionation process. • Low-frequency supplement of N 2 H 4 was beneficial for anammox stable operation. [ABSTRACT FROM AUTHOR]

Abstract: Tropomyosin is a two-chained α-helical coiled coil that binds along the length of the actin filament and regulates its function. The paper addresses the question of how a “simple” coiled-coil sequence encodes the information for binding and regulating the actin filament, its universal target. Determination of the tropomyosin sequence confirmed Crick’s predicted heptapeptide repeat of hydrophobic interface residues and revealed additional features that have been shown to be important for its function: a 7-fold periodicity predicted to correspond to actin binding sites and interruptions of the canonical interface with destabilizing residues, such as Ala. Evidence from published work is summarized, leading to the proposal of a paradigm that binding of tropomyosin to the actin filament requires local instability as well as regions of flexibility. The flexibility derives from bends and local unfolding at regions with a destabilized coiled-coil interface, as well as from the dynamic end-to-end complex. The features are required for tropomyosin to assume the form of the helical actin filament, and to bind to actin monomers along its length. The requirement of instability/flexibility for binding may be generalized to the binding of other coiled coils to their targets. [Copyright &y& Elsevier]