PyRETIS 3: Conquering rare and slow events without boundaries.

We present and discuss the advancements made in PyRETIS 3, the third instalment of our Python library for an efficient and user-friendly rare event simulation, focused to execute molecular simulations with replica exchange transition interface sampling (RETIS) and its variations. Apart from a general rewiring of the internal code towards a more modular structure, several recently developed sampling strategies have been implemented. These include recently developed Monte Carlo moves to increase path decorrelation and convergence rate, and new ensemble definitions to handle the challenges of long-lived metastable states and transitions with unbounded reactant and product states.

Highly parallelizable path sampling with minimal rejections using asynchronous replica exchange and infinite swaps.

Capturing rare yet pivotal events poses a significant challenge for molecular simulations. Path sampling provides a unique approach to tackle this issue without altering the potential energy landscape or dynamics, enabling recovery of both thermodynamic and kinetic information. However, despite its exponential acceleration compared to standard molecular dynamics, generating numerous trajectories can still require a long time.

Path sampling with memory reduction and replica exchange to reach long permeation timescales.

Assessing kinetics in biological processes with molecular dynamics simulations remains a computational and conceptual challenge, given the large time and length scales involved. For kinetic transport of biochemical compounds or drug molecules, the permeability through the phospholipid membranes is a key kinetic property, but long timescales are hindering the accurate computation. Technological advances in high-performance computing therefore need to be accompanied by theoretical and methodological developments.

Enhanced path sampling using subtrajectory Monte Carlo moves.

Path sampling allows the study of rare events, such as chemical reactions, nucleation, and protein folding, via a Monte Carlo (MC) exploration in path space. Instead of configuration points, this method samples short molecular dynamics (MD) trajectories with specific start- and end-conditions. As in configuration MC, its efficiency highly depends on the types of MC moves.

Exchanging Replicas with Unequal Cost, Infinitely and Permanently.

We developed a replica exchange method that is effectively parallelizable even if the computational cost of the Monte Carlo moves in the parallel replicas are considerably different, for instance, because the replicas run on different types of processor units or because of the algorithmic complexity. To prove detailed-balance, we make a paradigm shift from the common conceptual viewpoint in which the set of parallel replicas represents a high-dimensional superstate, to an ensemble-based criterion in which the other ensembles represent an environment that might or might not participate in the Monte Carlo move. In addition, based on a recent algorithm for computing permanents, we effectively increase the exchange rate to infinite without the steep factorial scaling as a function of the number of replicas.

The role of pressure and defects in the wurtzite to rock salt transition in cadmium selenide.

Using molecular dynamics and path sampling techniques we investigated the effect of pressure and defects in the wurtzite to rock salt transition in cadmium selenide (CdSe). In the pressure range 2-10 GPa, rate constants of transition are in the order of 10 to 10 s for the transformation of a relatively small wurtzite crystal consisting of 1024 atoms with periodic boundary conditions. The transition paths predominantly evolve through an intermediate 5-coordinated structure, as reported before, though its typical lifetime within the transition paths is particularly long in the intermediate pressure range (4-6 GPa).

Permeation Rates of Oxygen through a Lipid Bilayer Using Replica Exchange Transition Interface Sampling.

Several simulations strategies have emerged to predict the permeability of solutes across membranes, which is important for many biological or industrial processes such as drug design. The widespread inhomogeneous solubility-diffusion (ISD) model is based on the Smoluchowski equation and describes permeation as purely diffusive. The counting method, which counts membrane transitions in a long molecular dynamics (MD) trajectory, is free of this diffusive assumption, but it lacks sufficient statistics when the permeation involves high free energy barriers.

PyRETIS 2: An improbability drive for rare events.

The algorithmic development in the field of path sampling has made tremendous progress in recent years. Although the original transition path sampling method was mostly used as a qualitative tool to sample reaction paths, the more recent family of interface-based path sampling methods has paved the way for more quantitative rate calculation studies. Of the exact methods, the replica exchange transition interface sampling (RETIS) method is the most efficient, but rather difficult to implement.

Multiscale partial charge estimation on graphene for neutral, doped and charged flakes.

The minimal-basis iterative stockholder (MBIS) and restrained electrostatic potential (RESP) methods were applied to examine the effects of edges and of nitrogen and boron dopants on the atomic partial charges of neutral and charged graphene flakes. The results provided the parameters to fit a second-order atom-condensed Kohn-Sham DFT model (ACKS2), accurately determining the partial charges, the dipole and local electric fields in large graphene flakes with negligible cost. Our approach can lead to improvements of graphene force fields in charged conditions and guide the design of media for catalytic applications.

Diffusion of gas mixtures in the sI hydrate structure.

Replacing methane with carbon dioxide in gas hydrates has been suggested as a way of harvesting methane, while at the same time storing carbon dioxide. Experimental evidence suggests that this process is facilitated if gas mixtures are used instead of pure carbon dioxide. We studied the free energy barriers for diffusion of methane, carbon dioxide, nitrogen, and hydrogen in the sI hydrate structure using molecular simulation techniques.

Improving the mesoscopic modeling of DNA denaturation dynamics.

Although previously developed mesoscopic DNA models have successfully reproduced thermodynamic denaturation data, recent studies show that these overestimate the rate of denaturation by orders of magnitude. Using adapted Peyrard-Bishop-Dauxois (PBD) models, we have calculated the denaturation rates of several DNA hairpins and made comparison with experimental data. We show that the addition of a barrier at the onsite potential of the PBD model gives a more accurate description of the unzipping dynamics of short DNA sequences.

Local initiation conditions for water autoionization.

The pH of liquid water is determined by the infrequent process in which water molecules split into short-lived hydroxide and hydronium ions. This reaction is difficult to probe experimentally and challenging to simulate. One of the open questions is whether the local water structure around a slightly stretched OH bond is actually initiating the eventual breakage of this bond or whether this event is driven by a global ordering that involves many water molecules far away from the reaction center.

Foundations and latest advances in replica exchange transition interface sampling.

Nearly 20 years ago, transition path sampling (TPS) emerged as an alternative method to free energy based approaches for the study of rare events such as nucleation, protein folding, chemical reactions, and phase transitions. TPS effectively performs Monte Carlo simulations with relatively short molecular dynamics trajectories, with the advantage of not having to alter the actual potential energy surface nor the underlying physical dynamics. Although the TPS approach also introduced a methodology to compute reaction rates, this approach was for a long time considered theoretically attractive, providing the exact same results as extensively long molecular dynamics simulations, but still expensive for most relevant applications.

Fast Decorrelating Monte Carlo Moves for Efficient Path Sampling.

Many relevant processes in chemistry, physics, and biology are rare events from a computational perspective as they take place beyond the accessible time scale of molecular dynamics (MD). Examples are chemical reactions, nucleation, and conformational changes of biomolecules. Path sampling is an approach to break this time scale limit via a Monte Carlo (MC) sampling of MD trajectories.

PyRETIS: A well-done, medium-sized python library for rare events.

Transition path sampling techniques are becoming common approaches in the study of rare events at the molecular scale. More efficient methods, such as transition interface sampling (TIS) and replica exchange transition interface sampling (RETIS), allow the investigation of rare events, for example, chemical reactions and structural/morphological transitions, in a reasonable computational time. Here, we present PyRETIS, a Python library for performing TIS and RETIS simulations.

Rare event simulations reveal subtle key steps in aqueous silicate condensation.

A replica exchange transition interface sampling (RETIS) study combined with Born-Oppenheimer molecular dynamics (BOMD) is used to investigate the dynamics, thermodynamics and the mechanism of the early stages of the silicate condensation process. In this process, two silicate monomers, of which one is an anionic species, form a negatively charged five-coordinated silicate dimer. In a second stage, this dimer can fall apart again, forming the original monomers, or release a water molecule into the solution.

Analyzing Complex Reaction Mechanisms Using Path Sampling.

We introduce an approach to analyze collective variables (CVs) regarding their predictive power for a reaction. The method is based on already available path sampling data produced by, for instance, transition interface sampling or forward flux sampling, which are path sampling methods used for efficient computation of reaction rates. By a search in CV space, a measure of predictiveness can be optimized and, in addition, the number of CVs can be reduced using projection operations which keep this measure invariant.

Gluing potential energy surfaces with rare event simulations.

We develop a new method combining replica exchange transition interface sampling with two distinct potential energy surfaces. The method can be used to combine different levels of theory in a simulation of a molecular process (e.g.

A test on reactive force fields for the study of silica dimerization reactions.

We studied silica dimerization reactions in the gas and aqueous phase by density functional theory (DFT) and reactive force fields based on two parameterizations of ReaxFF. For each method (both ReaxFF force fields and DFT), we performed constrained geometry optimizations, which were subsequently evaluated in single point energy calculations using the other two methods. Standard fitting procedures typically compare the force field energies and geometries with those from quantum mechanical data after a geometry optimization.

Density Functional Theory Study on the Interactions of Metal Ions with Long Chain Deprotonated Carboxylic Acids.

In this work, interactions between carboxylate ions and calcium or sodium ions are investigated via density functional theory (DFT). Despite the ubiquitous presence of these interactions in natural and industrial chemical processes, few DFT studies on these systems exist in the literature. Special focus has been placed on determining the influence of the multibody interactions (with up to 4 carboxylates and one metal ion) on an effective pair-interaction potential, such as those used in molecular mechanics (MM).

Ab Initio Molecular Dynamics Study on the Interactions between Carboxylate Ions and Metal Ions in Water.

The interaction between a carboxylate anion (deprotonated propanoic acid) and the divalent Mg(2+), Ca(2+), Sr(2+), Ba(2+) metal ions is studied via ab initio molecular dynamics. The main focus of the study is the selectivity of the carboxylate-metal ion interaction in aqueous solution. The interaction is modeled by explicitly accounting for the solvent molecules on a DFT level.

Mesoscopic modeling of DNA denaturation rates: Sequence dependence and experimental comparison.

Using rare event simulation techniques, we calculated DNA denaturation rate constants for a range of sequences and temperatures for the Peyrard-Bishop-Dauxois (PBD) model with two different parameter sets. We studied a larger variety of sequences compared to previous studies that only consider DNA homopolymers and DNA sequences containing an equal amount of weak AT- and strong GC-base pairs. Our results show that, contrary to previous findings, an even distribution of the strong GC-base pairs does not always result in the fastest possible denaturation.

Low barriers for hydrogen diffusion in sII clathrate.

The transport of gas molecules in hydrates is presently poorly understood. In sII structured hydrates with hydrogen guests there is, for instance, a mismatch between experimental and computed values for diffusion constants. We provide an explanation for the experimentally observed diffusion rates, using DFT-based molecular dynamics simulations at 100 K.

Heat and mass transfer across interfaces in complex nanogeometries.

Heat and mass transfer in nanodevices depends much on the geometry due to the strong influence of curvature on interfacial properties, such as the Kapitza resistance. We present a method which combines nonequilibrium square gradient theory and nonequilibrium molecular dynamics simulations to obtain the coefficients in a curvature expansion of the interface transfer coefficients. The expansion can be used directly to describe heat and mass transfer in complex nanogeometries.

Enantioselective adsorption of ibuprofen and lysine in metal-organic frameworks.

This study reveals the efficient enantiomeric separation of bioactive molecules in the liquid phase. Chiral structure HMOF-1 separates racemic mixtures whereas heteroselectivity is observed for scalemic mixtures of ibuprofen using non-chiral MIL-47 and MIL-53. Lysine enantiomers are only separated by HMOF-1.