Machine learning–driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins

RAS is a signaling protein associated with the cell membrane that is mutated in up to 30% of human cancers. RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell membrane. Investigating such a mechanism requires near-atomistic detail at macroscopic temporal and spatial scales, which is not possible with conventional computational or experimental techniques. We demonstrate here a multiscale simulation infrastructure that uses machine learning to create a scale-bridging ensemble of over 100,000 simulations of active wild-type KRAS on a complex, asymmetric membrane. Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. We report distinctive patterns of local lipid composition that correlate with interfacially promiscuous RAS multimerization. These lipid fingerprints are coupled to RAS dynamics, predicted to influence effector binding, and therefore may be a mechanism for regulating cell signaling cascades.

Alkali Cation Effect on CO2 Electroreduction to CO: A Local Colligative Property

Converting carbon dioxide (CO2) into valuable products is one of the most important processes for a sustainable society. Especially, the electrochemical CO2 reduction reaction (CO2RR) offers an effective means, but its reaction mechanism is not yet fully understood. Here, we demonstrate that cation-coupled electron transfer (CCET) is a rate-determining step in the CO2RR to carbon monoxide. The first-principles-based multiscale simulation identifies a single cation that coordinates a CO2− intermediate adsorbed on Ag electrode. The CCET is experimentally verified by a collapse of the CO2RR polarization curves upon correcting Nernstianly for a bulk cation concentration. As further confirmation, a kinetic study shows that the CO2RR obeys first-order kinetics on a local cation concentration. Finally, this work unveils that the cation effect on CO2RR originates from the local colligative property, and further highlights the importance of ion-pairing tendency for electrochemical interface design to achieve high-performance CO2 electrolysis.

Alkali Cation Effect on CO2 Electroreduction to CO: A Local Colligative Property

Converting carbon dioxide (CO2) into valuable products is one of the most important processes for a sustainable society. Especially, the electrochemical CO2 reduction reaction (CO2RR) offers an effective means, but its reaction mechanism is not yet fully understood. Here, we demonstrate that cation-coupled electron transfer (CCET) is a rate-determining step in the CO2RR to carbon monoxide. The first-principles-based multiscale simulation identifies a single cation that coordinates a CO2− intermediate adsorbed on Ag electrode. The CCET is experimentally verified by a collapse of the CO2RR polarization curves upon correcting Nernstianly for a bulk cation concentration. As further confirmation, a kinetic study shows that the CO2RR obeys first-order kinetics on a local cation concentration. Finally, this work unveils that the cation effect on CO2RR originates from the local colligative property, and further highlights the importance of ion-pairing tendency for electrochemical interface design to achieve high-performance CO2 electrolysis.

Multiscale Simulation of Temperature- and Pressure-dependent Nonlinear Dynamics of PMMA/CNT Composite Plates

Owing to the excellent mechanical properties, polymethyl methacrylate (PMMA)/carbon nanotube (CNT) composite has been increasingly adopted in the aerospace field, which is usually subjected to various temperature conditions and supersonic aerodynamic loads. Using a molecular dynamics (MD)-based multiscale simulation, the nonlinear forced vibration of PMMA/CNT composite plate is investigated under coupled temperature and aerodynamic loads conditions. The longitudinal, transverse, and shear moduli of PMMA/single-walled CNT (SWCNT) nanocomposite obtained from MD simulation at different temperature and pressure levels are substituted into the extended rule of mixtures to establish the constitutive equations of PMMA/CNT composite plate. Meanwhile, Poisson’s ratio and thermal expansion coefficient of nanocomposite are used in the constitutive equations. Based on the third-order shear deformation theory, von-Karman nonlinear strain-displacement relation, and Hamilton’s principle, the partial differential equation of composite plate is derived, which is reduced into a set of coupled ordinary differential equations by applying Galerkin method and is solved using the fourth-order Runge-Kutta method. The phase portraits and time histories of composite plate are obtained under the complex loads including transverse harmonic excitation and aerodynamic pressure, which are applied to analyze the dynamic characteristics of system. This study reveals the nonlinear dynamic characteristics of PMMA/CNT composite plate, which contributes to the prediction of long-term performance of composite materials in aerospace field.