Blind search for complex chemical pathways using Harmonic Linear Discriminant Analysis

Abstract

Disentangling the mechanistic details of a chemical reaction pathway is a hard problem that often requires a considerable amount of chemical intuition and a component of luck. Experiments struggle in observing short-life metastable intermediates, while computer simulations often rely upon a good initial guess. In this work, we propose a method that, from the simulations of a reactant and a product state, searches for reaction mechanisms connecting the two by exploring the configuration space through metadynamics, a well known enhanced molecular dynamics method. The key quantity underlying this search is based on the use of an approach called Harmonic Linear Discriminant Analysis which allows a systematic construction of collective variables. Given the reactant and product states, we choose a set of descriptors capable of discriminating between the two states. In order not to prejudge the results, generic descriptors are introduced. The fluctuations of the descriptors in the two states are used to construct collective variables. We use metadynamics in an exploratory mode to discover the intermediates and the transition states that lead from reactant to product. The search is at first conducted at a low theory level. The calculation is then refined and the energy of the intermediates and transition states discovered during metadynamics is computed again using a higher level of theory. The method's aim is to offer a simple reaction mechanism search procedure that helps in saving time and is able to find unexpected mechanisms that defy well established chemical paradigms. We apply it to two reactions, showing that a high level of complexity can be hidden even in seemingly trivial and small systems. The method can be applied to larger systems, such as reactions in solution or catalysis.

References in corpus (10)

• Canonical sampling through velocity-rescaling
• Escaping free-energy minima
• PLUMED 2: New feathers for an old bird
• Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
• String Method for the Study of Rare Events
• Exploration of Reaction Pathways and Chemical Transformation Networks
• Heuristics-Guided Exploration of Reaction Mechanisms
• Folding a Small Protein Using Harmonic Linear Discriminant Analysis
• Finding Efficient Collective Variables: The Case of Crystallization
• The onset of dehydrogenation in solid Ammonia Borane, an ab-initio metadynamics study

Cited by in corpus (11)

• Data-Driven Collective Variables for Enhanced Sampling
• The Exploration of Chemical Reaction Networks
• Chemoton 2.0: Autonomous Exploration of Chemical Reaction Networks
• Autonomous Reaction Network Exploration in Homogeneous and Heterogeneous Catalysis
• From enhanced sampling to reaction profiles
• Deep Learning Collective Variables from Transition Path Ensemble
• Navigating chemical reaction space with a steering wheel
• Nucleating a Different Coordination in a Crystal under Pressure: A Study of the B1-B2 Transition in NaCl by Metadynamics
• Collective Variables for Conformational Polymorphism in Molecular Crystals
• Enhanced Sampling for Free Energy Profiles with Post-Transition-State Bifurcations
• Guiding Peptide Kinetics via Collective-Variable Tuning of Free-Energy Barriers