Inhibitors that disrupt the Ras-SOS1 interaction have been designed; the conformational details uncovered here may assist in the design of polypeptides inhibiting Grb2-SOS1 interaction, thus SOS1 recruitment to the membrane where Ras resides.We derive the exact steady-state solutions for the simplest model systems of resonant tunneling and tunneling with destructive quantum interference from the driven Liouville-von Neumann (DLvN) approach. Under the finite-state lead condition (the two electrodes have finite states), we analyze the asymptotic behavior of the steady-state current in the two limits of electronic relaxation. Under the infinite-state lead condition, the steady-state solutions of the two model systems can be cast as Landauer-type current formulas. According to the formulas, we show that the transmission functions near the resonant peak and the antiresonant dip can be significantly influenced by electronic relaxation in the electrodes. Moreover, under intermediate and strong electronic relaxation conditions, we analytically show that the steady-state current of the DLvN approach dramatically deviates from the Landauer current when destructive quantum interference occurs. In the regime of zero electronic relaxation, our results are reduced to the Landauer formula, indicating that the DLvN approach is equivalent to the Landauer approach when the leads have infinite states without any electronic relaxation.The emergence of machine learning methods in quantum chemistry provides new methods to revisit an old problem Can the predictive accuracy of electronic structure calculations be decoupled from their numerical bottlenecks? Previous attempts to answer this question have, among other methods, given rise to semi-empirical quantum chemistry in minimal basis representation. We present an adaptation of the recently proposed SchNet for Orbitals (SchNOrb) deep convolutional neural network model [K. T. Schütt et al., Nat. Commun. 10, 5024 (2019)] for electronic wave functions in an optimized quasi-atomic minimal basis representation. For five organic molecules ranging from 5 to 13 heavy atoms, the model accurately predicts molecular orbital energies and wave functions and provides access to derived properties for chemical bonding analysis. Particularly for larger molecules, the model outperforms the original atomic-orbital-based SchNOrb method in terms of accuracy and scaling. We conclude by discussing the future potential of this approach in quantum chemical workflows.NAMDis a molecular dynamics program designed for high-performance simulations of very large biological objects on CPU- and GPU-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS, and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics; controlling the temperature, pressure, and pH; applying external potentials on tailored grids; leveraging massively parallel resources in multiple-copy simulations; and hybrid quantum-mechanical/molecular-mechanical descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts toward achieving optimal performance on GPU-based architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run, and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.We show how to bound and calculate the likelihood of dynamical large deviations using evolutionary reinforcement learning. An agent, a stochastic model, propagates a continuous-time Monte Carlo trajectory and receives a reward conditioned upon the values of certain path-extensive quantities. Evolution produces progressively fitter agents, potentially allowing the calculation of a piece of a large-deviation rate function for a particular model and path-extensive quantity. For models with small state spaces, the evolutionary process acts directly on rates, and for models with large state spaces, the process acts on the weights of a neural network that parameterizes the model's rates. This approach shows how path-extensive physics problems can be considered within a framework widely used in machine learning.Active matter agents consume internal energy or extract energy from the environment for locomotion and force generation. Already, rather generic models, such as ensembles of active Brownian particles, exhibit phenomena, which are absent at equilibrium, particularly motility-induced phase separation and collective motion. Further intriguing nonequilibrium effects emerge in assemblies of bound active agents as in linear polymers or filaments. The interplay of activity and conformational degrees of freedom gives rise to novel structural and dynamical features of individual polymers, as well as in interacting ensembles. Such out-of-equilibrium polymers are an integral part of living matter, ranging from biological cells with filaments propelled by motor proteins in the cytoskeleton and RNA/DNA in the transcription process to long swarming bacteria and worms such as Proteus mirabilis and Caenorhabditis elegans, respectively. https://www.selleckchem.com/products/edralbrutinib.html Even artificial active polymers have been synthesized. The emergent properties of active polymers or filaments depend on the coupling of the active process to their conformational degrees of freedom, aspects that are addressed in this article.

Last-modified: 2024-09-10 (火) 22:49:14