Kinetic Constraints in the Specific Interaction between Phosphorylated Ubiquitin and Proteasomal Shuttle Factors

Ubiquitin (Ub) specifically interacts with the Ub-associating domain (UBA) in a proteasomal shuttle factor, while the latter is involved in either proteasomal targeting or self-assembly coacervation. PINK1 phosphorylates Ub at S65 and makes Ub alternate between C-terminally relaxed (pUbRL) and retracted conformations (pUbRT). Using NMR spectroscopy, we show that pUbRL but not pUbRT preferentially interacts with the UBA from two proteasomal shuttle factors Ubqln2 and Rad23A. Yet discriminatorily, Ubqln2-UBA binds to pUb more tightly than Rad23A does and selectively enriches pUbRL upon complex formation. Further, we determine the solution structure of the complex between Ubqln2-UBA and pUbRL and uncover the thermodynamic basis for the stronger interaction. NMR kinetics analysis at different timescales further suggests an indued-fit binding mechanism for pUb-UBA interaction. Notably, at a relatively low saturation level, the dissociation rate of the UBA-pUbRL complex is comparable with the exchange rate between pUbRL and pUbRT. Thus, a kinetic constraint would dictate the interaction between Ub and UBA, thus fine-tuning the functional state of the proteasomal shuttle factors.

Kinetically-constrained ring-polymer molecular dynamics for non-adiabatic chemistries involving solvent and donor–acceptor dynamical effects

We investigate the performance of the recently developed kinetically-constrained ring polymer molecular dynamics (KC-RPMD) method for the description of model condensed-phase electron transfer (ET) reactions in which solvent and donor–acceptor dynamics play an important role. Comparison of KC-RPMD with results from Golden-Rule rate theories and numerically exact quantum dynamics calculations demonstrates that KC-RPMD accurately captures the combination of electronic- and nuclear-dynamical effects throughout the Marcus (intermediate solvent friction) and Zusman (large solvent friction) regimes of ET. It is also demonstrated that KC-RPMD accurately describes systems in which the magnitude of the diabatic coupling depends on the position of a dynamical donor–acceptor mode. In addition to these successes, however, we present an unsurprising failure of KC-RPMD to capture the enhancement of the ET rate in the low solvent friction regime associated with nuclear coherence effects. In this analysis, we re-visit several aspects of the original KC-RPMD formulation, including the form of the kinetic constraint and the choice of the mass of the auxiliary electronic variable. In particular, we introduce a Langevin bath for the auxiliary electronic variable to correct for its unphysically low coupling with the nuclear degrees of freedom. This work demonstrates that the KC-RPMD method is well suited for the direct simulation of non-adiabatic donor–acceptor chemistries associated with many complex systems, including those for which solvent dynamics plays an important role in the reaction mechanism.

Modelling of Oxidation of Fe-Ni-Cr Alloys

Mathematical model of selective and competitive oxidation of multi-component non ideal alloys is used for modelling oxidation of Fe-Cr-Ni alloys. The model is based on: a) the Danielewski-Holly model of interdiffusion, b) the Wagner model of the Ni-Pt alloy oxidation, c) the postulate that the values of fluxes in reacting alloy are limited (the kinetic constraint) and d) the thermodynamics of the Fe-Ni-Cr system. In this paper for the first time modelling of oxidation of a ternary non-ideal alloy based on Danielewski-Holly model is presented. The model is used to predict the evolution of component distributions in the reacting ternary Fe-Cr-Ni alloy. The results of the modelling of oxidation of the 316L stainless steel at 1173 K are presented. We compute the chromium depletion during the long term oxidation. The results allows to conclude that the oxidation reaction is limited by interdiffusion in reacting alloy. The computations demonstrate that the chromium depletion is the key factor affecting the scale stability during the long time exposition.

DYNAMICAL NON-LINEAR SUSCEPTIBILITY OF THE QUENCHED AND ANNEALED FRUSTRATED LATTICE GAS MODELS

In this paper we study the 3D frustrated lattice gas model in the quenched and annealed versions. In the first case, the dynamical non-linear susceptibility grows monotonically as a function of time, until reaching a plateau that corresponds to the static value. The static non-linear susceptibility diverges at some density, signaling the presence of a thermodynamical transition. In the annealed version, where the disorder is allowed to evolve in time with a suitable kinetic constraint, the thermodynamics of the model is trivial, and the static non-linear susceptibility does not show any singularity. Nevertheless, the model shows a maximum in the dynamical non-linear susceptibility at a characteristic value of the time. Approaching the density corresponding to the singularity of the quenched model, both the maximum and the characteristic time diverge. We conclude that the critical behavior of the dynamical susceptibility in the annealed model is related to the divergence of the static susceptibility in the quenched case. This suggests a similar mechanism also in supercooled glass-forming liquids, where an analogous behavior in the dynamical non-linear susceptibility is observed.