18 research outputs found
Exploration of Reaction Pathways and Chemical Transformation Networks
For the investigation of chemical reaction networks, the identification of
all relevant intermediates and elementary reactions is mandatory. Many
algorithmic approaches exist that perform explorations efficiently and
automatedly. These approaches differ in their application range, the level of
completeness of the exploration, as well as the amount of heuristics and human
intervention required. Here, we describe and compare the different approaches
based on these criteria. Future directions leveraging the strengths of chemical
heuristics, human interaction, and physical rigor are discussed.Comment: 48 pages, 4 figure
Heuristics-Guided Exploration of Reaction Mechanisms
For the investigation of chemical reaction networks, the efficient and
accurate determination of all relevant intermediates and elementary reactions
is mandatory. The complexity of such a network may grow rapidly, in particular
if reactive species are involved that might cause a myriad of side reactions.
Without automation, a complete investigation of complex reaction mechanisms is
tedious and possibly unfeasible. Therefore, only the expected dominant reaction
paths of a chemical reaction network (e.g., a catalytic cycle or an enzymatic
cascade) are usually explored in practice. Here, we present a computational
protocol that constructs such networks in a parallelized and automated manner.
Molecular structures of reactive complexes are generated based on heuristic
rules derived from conceptual electronic-structure theory and subsequently
optimized by quantum chemical methods to produce stable intermediates of an
emerging reaction network. Pairs of intermediates in this network that might be
related by an elementary reaction according to some structural similarity
measure are then automatically detected and subjected to an automated search
for the connecting transition state. The results are visualized as an
automatically generated network graph, from which a comprehensive picture of
the mechanism of a complex chemical process can be obtained that greatly
facilitates the analysis of the whole network. We apply our protocol to the
Schrock dinitrogen-fixation catalyst to study alternative pathways of catalytic
ammonia production.Comment: 27 pages, 9 figure
Flow Annealed Importance Sampling Bootstrap
Normalizing flows are tractable density models that can approximate
complicated target distributions, e.g. Boltzmann distributions of physical
systems. However, current methods for training flows either suffer from
mode-seeking behavior, use samples from the target generated beforehand by
expensive MCMC simulations, or use stochastic losses that have very high
variance. To avoid these problems, we augment flows with annealed importance
sampling (AIS) and minimize the mass covering -divergence with
, which minimizes importance weight variance. Our method, Flow AIS
Bootstrap (FAB), uses AIS to generate samples in regions where the flow is a
poor approximation of the target, facilitating the discovery of new modes. We
target with AIS the minimum variance distribution for the estimation of the
-divergence via importance sampling. We also use a prioritized buffer
to store and reuse AIS samples. These two features significantly improve FAB's
performance. We apply FAB to complex multimodal targets and show that we can
approximate them very accurately where previous methods fail. To the best of
our knowledge, we are the first to learn the Boltzmann distribution of the
alanine dipeptide molecule using only the unnormalized target density and
without access to samples generated via Molecular Dynamics (MD) simulations:
FAB produces better results than training via maximum likelihood on MD samples
while using 100 times fewer target evaluations. After reweighting samples with
importance weights, we obtain unbiased histograms of dihedral angles that are
almost identical to the ground truth ones
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A Bayesian approach to calibrating high-throughput virtual screening results and application to organic photovoltaic materials
A novel approach for calibrating quantum-chemical properties determined as part of a high-throughput virtual screen to experimental analogs is presented. Information on the molecular graph is extracted through the use of extended connectivity fingerprints, and exploited using a Gaussian process to calibrate both electronic properties such as frontier orbital energies, and optical gaps and device properties such as short circuit current density, open circuit voltage and power conversion efficiency. The Bayesian nature of this process affords a value for uncertainty in addition to each calibrated value. This allows the researcher to gain intuition about the model as well as the ability to respect its bounds.Chemistry and Chemical Biolog
Error Assessment of Computational Models in Chemistry
Computational models in chemistry rely on a number of approximations. The effect of such approximations on observables derived from them is often unpredictable. Therefore, it is challenging to quantify the uncertainty of a computational result, which, however, is necessary to assess
the suitability of a computational model. Common performance statistics such as the mean absolute error are prone to failure as they do not distinguish the explainable (systematic) part of the errors from their unexplainable (random) part. In this paper, we discuss problems and solutions for
performance assessment of computational models based on several examples from the quantum chemistry literature. For this purpose, we elucidate the different sources of uncertainty, the elimination of systematic errors, and the combination of individual uncertainty components to the uncertainty of a prediction
Systematic Error Estimation for Chemical Reaction Energies
For a theoretical
understanding of the reactivity of complex chemical
systems, accurate relative energies between intermediates and transition
states are required. Despite its popularity, density functional theory
(DFT) often fails to provide sufficiently accurate data, especially
for molecules containing transition metals. Due to the huge number
of intermediates that need to be studied for all but the simplest
chemical processes, DFT is, to date, the only method that is computationally
feasible. Here, we present a Bayesian framework for DFT that allows
for error estimation of calculated properties. Since the optimal choice
of parameters in present-day density functionals is strongly system
dependent, we advocate for a system-focused reparameterization. While,
at first sight, this approach conflicts with the first-principles
character of DFT that should make it, in principle, system independent,
we deliberately introduce system dependence to be able to assign a
stochastically meaningful error to the system-dependent parametrization,
which makes it nonarbitrary. By reparameterizing a functional that
was derived on a sound physical basis to a chemical system of interest,
we obtain a functional that yields reliable confidence intervals for
reaction energies. We demonstrate our approach on the example of catalytic
nitrogen fixation