Mechanism Deduction from Noisy Chemical Reaction Networks

We introduce KiNetX, a fully automated meta-algorithm for the kinetic analysis of complex chemical reaction networks derived from semi-accurate but efficient electronic structure calculations. It is designed to (i) accelerate the automated exploration of such networks, and (ii) cope with model-inherent errors in electronic structure calculations on elementary reaction steps. We developed and implemented KiNetX to possess three features. First, KiNetX evaluates the kinetic relevance of every species in a (yet incomplete) reaction network to confine the search for new elementary reaction steps only to those species that are considered possibly relevant. Second, KiNetX identifies and eliminates all kinetically irrelevant species and elementary reactions to reduce a complex network graph to a comprehensible mechanism. Third, KiNetX estimates the sensitivity of species concentrations toward changes in individual rate constants (derived from relative free energies), which allows us to systematically select the most efficient electronic structure model for each elementary reaction given a predefined accuracy. The novelty of KiNetX consists in the rigorous propagation of correlated free-energy uncertainty through all steps of our kinetic analyis. To examine the performance of KiNetX, we developed AutoNetGen. It semirandomly generates chemistry-mimicking reaction networks by encoding chemical logic into their underlying graph structure. AutoNetGen allows us to consider a vast number of distinct chemistry-like scenarios and, hence, to discuss assess the importance of rigorous uncertainty propagation in a statistical context. Our results reveal that KiNetX reliably supports the deduction of product ratios, dominant reaction pathways, and possibly other network properties from semi-accurate electronic structure data.Comment: 36 pages, 4 figures, 2 table

Kinetic Intersections as a Source of Information on Rate Coefficients

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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

Maximum Margin Clustering for State Decomposition of Metastable Systems

When studying a metastable dynamical system, a prime concern is how to decompose the phase space into a set of metastable states. Unfortunately, the metastable state decomposition based on simulation or experimental data is still a challenge. The most popular and simplest approach is geometric clustering which is developed based on the classical clustering technique. However, the prerequisites of this approach are: (1) data are obtained from simulations or experiments which are in global equilibrium and (2) the coordinate system is appropriately selected. Recently, the kinetic clustering approach based on phase space discretization and transition probability estimation has drawn much attention due to its applicability to more general cases, but the choice of discretization policy is a difficult task. In this paper, a new decomposition method designated as maximum margin metastable clustering is proposed, which converts the problem of metastable state decomposition to a semi-supervised learning problem so that the large margin technique can be utilized to search for the optimal decomposition without phase space discretization. Moreover, several simulation examples are given to illustrate the effectiveness of the proposed method

Modeling, Simulating, and Parameter Fitting of Biochemical Kinetic Experiments

In many chemical and biological applications, systems of differential equations containing unknown parameters are used to explain empirical observations and experimental data. The DEs are typically nonlinear and difficult to analyze, requiring numerical methods to approximate the solutions. Compounding this difficulty are the unknown parameters in the DE system, which must be given specific numerical values in order for simulations to be run. Estrogen receptor protein dimerization is used as an example to demonstrate model construction, reduction, simulation, and parameter estimation. Mathematical, computational, and statistical methods are applied to empirical data to deduce kinetic parameter estimates and guide decisions regarding future experiments and modeling. The process demonstrated serves as a pedagogical example of quantitative methods being used to extract parameter values from biochemical data models.Comment: 23 pages, 9 figures, to be published in SIAM Revie

Self-optimized construction of transition rate matrices from accelerated atomistic simulations with Bayesian uncertainty quantification

A massively parallel method to build large transition rate matrices from temperature accelerated molecular dynamics trajectories is presented. Bayesian Markov model analysis is used to estimate the expected residence time in the known state space, providing crucial uncertainty quantification for higher scale simulation schemes such as kinetic Monte Carlo or cluster dynamics. The estimators are additionally used to optimize where exploration is performed and the degree of temperature ac- celeration on the fly, giving an autonomous, optimal procedure to explore the state space of complex systems. The method is tested against exactly solvable models and used to explore the dynamics of C15 interstitial defects in iron. Our uncertainty quantification scheme allows for accurate modeling of the evolution of these defects over timescales of several seconds.Comment: 14 pages, 7 figure

Meta-heuristic algorithms in car engine design: a literature survey

Meta-heuristic algorithms are often inspired by natural phenomena, including the evolution of species in Darwinian natural selection theory, ant behaviors in biology, flock behaviors of some birds, and annealing in metallurgy. Due to their great potential in solving difficult optimization problems, meta-heuristic algorithms have found their way into automobile engine design. There are different optimization problems arising in different areas of car engine management including calibration, control system, fault diagnosis, and modeling. In this paper we review the state-of-the-art applications of different meta-heuristic algorithms in engine management systems. The review covers a wide range of research, including the application of meta-heuristic algorithms in engine calibration, optimizing engine control systems, engine fault diagnosis, and optimizing different parts of engines and modeling. The meta-heuristic algorithms reviewed in this paper include evolutionary algorithms, evolution strategy, evolutionary programming, genetic programming, differential evolution, estimation of distribution algorithm, ant colony optimization, particle swarm optimization, memetic algorithms, and artificial immune system