Skipping the Replica Exchange Ladder with Normalizing Flows.

We combine replica exchange (parallel tempering) with normalizing flows, a class of deep generative models. These two sampling strategies complement each other, resulting in an efficient method for sampling molecular systems characterized by rare events, which we call learned replica exchange (LREX). In LREX, a normalizing flow is trained to map the configurations of the fastest-mixing replica into configurations belonging to the target distribution, allowing direct exchanges between the two without the need to simulate intermediate replicas.

Rare Event Kinetics from Adaptive Bias Enhanced Sampling.

We introduce a novel enhanced sampling approach named on-the-fly probability enhanced sampling (OPES) flooding for calculating the kinetics of rare events from atomistic molecular dynamics simulation. This method is derived from the OPES approach [Invernizzi and Parrinello, 7, 2731-2736], which has been recently developed for calculating converged free energy surfaces for complex systems. In this paper, we describe the theoretical details of the OPES flooding technique and demonstrate the application on three systems of increasing complexity: barrier crossing in a two-dimensional double-well potential, conformational transition in the alanine dipeptide in the gas phase, and the folding and unfolding of the chignolin polypeptide in an aqueous environment.

Exploration vs Convergence Speed in Adaptive-Bias Enhanced Sampling.

In adaptive-bias enhanced sampling methods, a bias potential is added to the system to drive transitions between metastable states. The bias potential is a function of a few collective variables and is gradually modified according to the underlying free energy surface. We show that when the collective variables are suboptimal, there is an exploration-convergence tradeoff, and one must choose between a quickly converging bias that will lead to fewer transitions or a slower to converge bias that can explore the phase space more efficiently but might require a much longer time to produce an accurate free energy estimate.

A combined molecular dynamics and experimental study of two-step process enabling low-temperature formation of phase-pure α-FAPbI.

It is well established that the lack of understanding the crystallization process in a two-step sequential deposition has a direct impact on efficiency, stability, and reproducibility of perovskite solar cells. Here, we try to understand the solid-solid phase transition occurring during the two-step sequential deposition of methylammonium lead iodide and formamidinium lead iodide. Using metadynamics, x-ray diffraction, and Raman spectroscopy, we reveal the microscopic details of this process.

Attenuating the fermion sign problem in path integral Monte Carlo simulations using the Bogoliubov inequality and thermodynamic integration.

Accurate thermodynamic simulations of correlated fermions using path integral Monte Carlo (PIMC) methods are of paramount importance for many applications such as the description of ultracold atoms, electrons in quantum dots, and warm-dense matter. The main obstacle is the fermion sign problem (FSP), which leads to an exponential increase in computation time both with an increase in the system size and with a decrease in the temperature. Very recently, Hirshberg et al.

Path integral molecular dynamics for fermions: Alleviating the sign problem with the Bogoliubov inequality.

We present a method for performing path integral molecular dynamics (PIMD) simulations for fermions and address its sign problem. PIMD simulations are widely used for studying many-body quantum systems at thermal equilibrium. However, they assume that the particles are distinguishable and neglect bosonic and fermionic exchange effects.

Rethinking Metadynamics: From Bias Potentials to Probability Distributions.

Metadynamics is an enhanced sampling method of great popularity, based on the on-the-fly construction of a bias potential that is a function of a selected number of collective variables. We propose here a change in perspective that shifts the focus from the bias to the probability distribution reconstruction while retaining some of the key characteristics of metadynamics, such as flexible on-the-fly adjustments to the free energy estimate. The result is an enhanced sampling method that presents a drastic improvement in convergence speed, especially when dealing with suboptimal and/or multidimensional sets of collective variables.

Making the Best of a Bad Situation: A Multiscale Approach to Free Energy Calculation.

Many enhanced sampling techniques rely on the identification of a number of collective variables that describe all the slow modes of the system. By constructing a bias potential in this reduced space, one is then able to sample efficiently and reconstruct the free energy landscape. In methods such as metadynamics, the quality of these collective variables plays a key role in convergence efficiency.

Enhanced Sampling of Transition States.

The free energy landscapes of several fundamental processes are characterized by high barriers separating long-lived metastable states. In order to explore these type of landscapes, enhanced sampling methods are used. While many such methods are able to obtain sufficient sampling in order to draw the free energy, the transition states are often sparsely sampled.

Molecular dynamics simulations of liquid silica crystallization.

Silica is one of the most abundant minerals on Earth and is widely used in many fields. Investigating the crystallization of liquid silica by atomic simulations is of great importance to understand the crystallization mechanism; however, the high crystallization barrier and the tendency of silica to form glasses make such simulations very challenging. Here we have studied liquid silica crystallization to β-cristobalite with metadynamics, using X-ray diffraction (XRD) peak intensities as collective variables.

Coarse graining from variationally enhanced sampling applied to the Ginzburg-Landau model.

A powerful way to deal with a complex system is to build a coarse-grained model capable of catching its main physical features, while being computationally affordable. Inevitably, such coarse-grained models introduce a set of phenomenological parameters, which are often not easily deducible from the underlying atomistic system. We present a unique approach to the calculation of these parameters, based on the recently introduced variationally enhanced sampling method.