Flow-matching -- efficient coarse-graining of molecular dynamics without forces

Coarse-grained (CG) molecular simulations have become a standard tool to study molecular processes on time- and length-scales inaccessible to all-atom simulations. Parameterizing CG force fields to match all-atom simulations has mainly relied on force-matching or relative entropy minimization, which require many samples from costly simulations with all-atom or CG resolutions, respectively. Here we present flow-matching, a new training method for CG force fields that combines the advantages of both methods by leveraging normalizing flows, a generative deep learning method. Flow-matching first trains a normalizing flow to represent the CG probability density, which is equivalent to minimizing the relative entropy without requiring iterative CG simulations. Subsequently, the flow generates samples and forces according to the learned distribution in order to train the desired CG free energy model via force matching. Even without requiring forces from the all-atom simulations, flow-matching outperforms classical force-matching by an order of magnitude in terms of data efficiency, and produces CG models that can capture the folding and unfolding transitions of small proteins

Machine learning implicit solvation for molecular dynamics

Accurate modeling of the solvent environment for biological molecules is crucial for computational biology and drug design. A popular approach to achieve long simulation time scales for large system sizes is to incorporate the effect of the solvent in a mean-field fashion with implicit solvent models. However, a challenge with existing implicit solvent models is that they often lack accuracy or certain physical properties compared to explicit solvent models as the many-body effects of the neglected solvent molecules are difficult to model as a mean field. Here, we leverage machine learning (ML) and multi-scale coarse graining (CG) in order to learn implicit solvent models that can approximate the energetic and thermodynamic properties of a given explicit solvent model with arbitrary accuracy, given enough training data. Following the previous ML–CG models CGnet and CGSchnet, we introduce ISSNet, a graph neural network, to model the implicit solvent potential of mean force. ISSNet can learn from explicit solvent simulation data and be readily applied to molecular dynamics simulations. We compare the solute conformational distributions under different solvation treatments for two peptide systems. The results indicate that ISSNet models can outperform widely used generalized Born and surface area models in reproducing the thermodynamics of small protein systems with respect to explicit solvent. The success of this novel method demonstrates the potential benefit of applying machine learning methods in accurate modeling of solvent effects for in silico research and biomedical applications

Statistically Optimal Force Aggregation for Coarse-Graining Molecular Dynamics

Machine-learned coarse-grained (CG) models have the potential for simulating large molecular complexes beyond what is possible with atomistic molecular dynamics. However, training accurate CG models remains a challenge. A widely used methodology for learning CG force-fields maps forces from all-atom molecular dynamics to the CG representation and matches them with a CG force-field on average. We show that there is flexibility in how to map all-atom forces to the CG representation, and that the most commonly used mapping methods are statistically inefficient and potentially even incorrect in the presence of constraints in the all-atom simulation. We define an optimization statement for force mappings and demonstrate that substantially improved CG force-fields can be learned from the same simulation data when using optimized force maps. The method is demonstrated on the miniproteins Chignolin and Tryptophan Cage and published as open-source code.Comment: 44 pages, 19 figure

Topological edge and corner states in Bi fractals on InSb

Topological materials hosting metallic edges characterized by integer quantized conductivity in an insulating bulk have revolutionized our understanding of transport in matter. The topological protection of these edge states is based on symmetries and dimensionality. However, only integer-dimensional models have been classified, and the interplay of topology and fractals, which may have a non-integer dimension, remained largely unexplored. Quantum fractals have recently been engineered in metamaterials, but up to present no topological states were unveiled in fractals realized in real materials. Here, we show theoretically and experimentally that topological edge and corner modes arise in fractals formed upon depositing thin layers of bismuth on an indium antimonide substrate. Scanning tunneling microscopy reveals the appearance of (nearly) zero-energy modes at the corners of Sierpi\'nski triangles, as well as the formation of outer and inner edge modes at higher energies. Unexpectedly, a robust and sharp depleted mode appears at the outer and inner edges of the samples at negative bias voltages. The experimental findings are corroborated by theoretical calculations in the framework of a continuum muffin-tin and a lattice tight-binding model. The stability of the topological features to the introduction of a Rashba spin-orbit coupling and disorder is discussed. This work opens the perspective to novel electronics in real materials at non-integer dimensions with robust and protected topological states.Comment: Main manuscript 14 pages, supplementary material 34 page

Coarse graining molecular dynamics with graph neural networks

Coarse graining enables the investigation of molecular dynamics for larger systems and at longer timescales than is possible at an atomic resolution. However, a coarse graining model must be formulated such that the conclusions we draw from it are consistent with the conclusions we would draw from a model at a finer level of detail. It has been proved that a force matching scheme defines a thermodynamically consistent coarse-grained model for an atomistic system in the variational limit. Wang et al. [ACS Cent. Sci. 5, 755 (2019)] demonstrated that the existence of such a variational limit enables the use of a supervised machine learning framework to generate a coarse-grained force field, which can then be used for simulation in the coarse-grained space. Their framework, however, requires the manual input of molecular features to machine learn the force field. In the present contribution, we build upon the advance of Wang et al. and introduce a hybrid architecture for the machine learning of coarse-grained force fields that learn their own features via a subnetwork that leverages continuous filter convolutions on a graph neural network architecture. We demonstrate that this framework succeeds at reproducing the thermodynamics for small biomolecular systems. Since the learned molecular representations are inherently transferable, the architecture presented here sets the stage for the development of machine-learned, coarse-grained force fields that are transferable across molecular systems

Navigating protein landscapes with a machine-learned transferable coarse-grained model

The most popular and universally predictive protein simulation models employ all-atom molecular dynamics (MD), but they come at extreme computational cost. The development of a universal, computationally efficient coarse-grained (CG) model with similar prediction performance has been a long-standing challenge. By combining recent deep learning methods with a large and diverse training set of all-atom protein simulations, we here develop a bottom-up CG force field with chemical transferability, which can be used for extrapolative molecular dynamics on new sequences not used during model parametrization. We demonstrate that the model successfully predicts folded structures, intermediates, metastable folded and unfolded basins, and the fluctuations of intrinsically disordered proteins while it is several orders of magnitude faster than an all-atom model. This showcases the feasibility of a universal and computationally efficient machine-learned CG model for proteins

‘Cut and stick’ ion gels as effective dielectrics for synaptic transistors

With the development of biomimetic engineering, artificial synaptic devices are deemed of paramount importance in the future brain-inspired neuromorphic computational devices. Meanwhile, flexible electronics have received considerable interests. Here, an artificial synapse based on the thin film transistor gated by a flexible ion gel is proposed for the synaptic emulation. Short term synaptic plasticity, long term synaptic plasticity, filtering and spike time dependent plasticity are all experimentally demonstrated in the artificial synapse. More importantly, we find out that in contrast with the conventional silicon dioxide gates, stronger synaptic behaviors can be induced by the ‘cut and stick’ ion gels at a much lower energy consumption. Our results suggest that the foldable and transferable ion gels have the potential to be incorporated into the low energy, high density and flexible neuromorphic computing devices.Bachelor of Engineering (Materials Engineering