scholarly journals Reply to “Comment on ‘Reaction Coordinates and Pathways of Mechanochemical Transformations’”

2016 ◽  
Vol 120 (9) ◽  
pp. 2646-2647
Author(s):  
Stanislav M. Avdoshenko ◽  
Dmitrii E. Makarov
Keyword(s):  
Reaction Coordinates

Rare event simulation

2017 ◽  
Author(s):  
Michael P. Allen ◽  
Dominic J. Tildesley
Keyword(s):  
Rare Event ◽  
Path Sampling ◽  
Rapid Progress ◽  
Computationally Efficient ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Event Simulation ◽  
Reaction Coordinates ◽  
Simulation Techniques ◽  
Transition Interface

The development of techniques to simulate infrequent events has been an area of rapid progress in recent years. In this chapter, we shall discuss some of the simulation techniques developed to study the dynamics of rare events. A basic summary of the statistical mechanics of barrier crossing is followed by a discussion of approaches based on the identification of reaction coordinates, and those which seek to avoid prior assumptions about the transition path. The demanding technique of transition path sampling is introduced and forward flux sampling and transition interface sampling are considered as rigorous but computationally efficient approaches.

scholarly journals Dimensionality Reduction of Complex Metastable Systems via Kernel Embeddings of Transition Manifolds

2020 ◽  
Vol 31 (1) ◽  
Author(s):  
Andreas Bittracher ◽  
Stefan Klus ◽  
Boumediene Hamzi ◽  
Péter Koltai ◽  
Christof Schütte
Keyword(s):  
Stochastic Systems ◽  
Reproducing Kernel ◽  
Learning Algorithm ◽  
Reproducing Kernel Hilbert Space ◽  
Mathematical Framework ◽  
Reaction Coordinates ◽  
Effective Dynamics ◽  
Distortion Bounds ◽  
Low Dimensional ◽  
Metastable Systems

AbstractWe present a novel kernel-based machine learning algorithm for identifying the low-dimensional geometry of the effective dynamics of high-dimensional multiscale stochastic systems. Recently, the authors developed a mathematical framework for the computation of optimal reaction coordinates of such systems that is based on learning a parameterization of a low-dimensional transition manifold in a certain function space. In this article, we enhance this approach by embedding and learning this transition manifold in a reproducing kernel Hilbert space, exploiting the favorable properties of kernel embeddings. Under mild assumptions on the kernel, the manifold structure is shown to be preserved under the embedding, and distortion bounds can be derived. This leads to a more robust and more efficient algorithm compared to the previous parameterization approaches.

scholarly journals Data-driven computation of molecular reaction coordinates

2018 ◽  
Vol 149 (15) ◽  
pp. 154103 ◽  
Author(s):  
Andreas Bittracher ◽  
Ralf Banisch ◽  
Christof Schütte
Keyword(s):  
Data Driven ◽  
Reaction Coordinates ◽  
Molecular Reaction

scholarly journals Kinetics and Reaction Coordinates of the Reassembly of Protein Fragments Via Forward Flux Sampling

2010 ◽  
Vol 98 (9) ◽  
pp. 1911-1920 ◽  
Author(s):  
Ernesto E. Borrero ◽  
Lydia M. Contreras Martínez ◽  
Matthew P. DeLisa ◽  
Fernando A. Escobedo
Keyword(s):  
Protein Fragments ◽  
Reaction Coordinates

Three Dimensional Triply Resonant Sum Frequency Spectroscopy Revealing Vibronic Coupling in Cobalamins: Toward a Probe of Reaction Coordinates

2018 ◽  
Vol 122 (46) ◽  
pp. 9031-9042 ◽  
Author(s):  
Jonathan D. Handali ◽  
Kyle F. Sunden ◽  
Blaise J. Thompson ◽  
Nathan A. Neff-Mallon ◽  
Emily M. Kaufman ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Vibronic Coupling ◽  
Sum Frequency ◽  
Reaction Coordinates ◽  
Sum Frequency Spectroscopy

Major Improvements in Robustness and Efficiency during the Screening of Novel Enzyme Effectors by the 3-Point Kinetics Assay

2020 ◽  
pp. 247255522095838
Author(s):  
Maria Filipa Pinto ◽  
Francisco Figueiredo ◽  
Alexandra Silva ◽  
António R. Pombinho ◽  
Pedro José Barbosa Pereira ◽  
...  
Keyword(s):  
Initial Period ◽  
Drug Repurposing ◽  
False Positives ◽  
Success Rates ◽  
Reaction Coordinates ◽  
Enzyme Modulation ◽  
Point Analysis ◽  
Random Variability ◽  
Time Courses ◽  
Point Kinetics

The throughput level currently reached by automatic liquid handling and assay monitoring techniques is expected to facilitate the discovery of new modulators of enzyme activity. Judicious and dependable ways to interpret vast amounts of information are, however, required to effectively answer this challenge. Here, the 3-point method of kinetic analysis is proposed as a means to significantly increase the hit success rates and decrease the number of falsely identified compounds (false positives). In this post-Michaelis–Menten approach, each screened reaction is probed in three different occasions, none of which necessarily coincide with the initial period of constant velocity. Enzymology principles rather than subjective criteria are applied to identify unwanted outliers such as assay artifacts, and then to accurately distinguish true enzyme modulation effects from false positives. The exclusion and selection criteria are defined based on the 3-point reaction coordinates, whose relative positions along the time-courses may change from well to well or from plate to plate, if necessary. The robustness and efficiency of the new method is illustrated during a small drug repurposing screening of potential modulators of the deubiquinating activity of ataxin-3, a protein implicated in Machado–Joseph disease. Apparently, intractable Z factors are drastically enhanced after (1) eliminating spurious results, (2) improving the normalization method, and (3) increasing the assay resilience to systematic and random variability. Numerical simulations further demonstrate that the 3-point analysis is highly sensitive to specific, catalytic, and slow-onset modulation effects that are particularly difficult to detect by typical endpoint assays.

scholarly journals A QM/MM Study of Acylphosphatase Reveals the Nucleophilic-Attack and Ensuing Carbonyl-Assisted Catalytic Mechanisms

2020 ◽  
Author(s):  
zheng zhao ◽  
Phil bourne ◽  
Hao Hu ◽  
Huanyu Chu
Keyword(s):  
Energy Barrier ◽  
Potential Energy Surfaces ◽  
Catalytic Mechanism ◽  
Interaction Networks ◽  
Nucleophilic Attack ◽  
Reaction Coordinates ◽  
Transition State Stabilization ◽  
Catalytic Mechanisms ◽  
Energy Surfaces

Acylphosphatase is one of the vital enzymes in many organs/tissues to catalyze an acylphosphate molecule into carboxylate and phosphate. Here we use a combined <i>ab initio</i> QM/MM approach to reveal the catalytic mechanism of the benzoylphosphate-bound acylphosphatase system. Using a multi-dimensional reaction-coordinates-driving scheme, we obtained a detailed catalytic process including one nucleophilic-attack and then an ensuing carbonyl-shuttle catalytic mechanism by calculating two-dimensional potential energy surfaces. We also obtained an experiment-agreeable energy barrier and validated the role of the key amino acid Asn38. Additionally, we qualified the transition state stabilization strategy based on the amino acids-contributed interaction networks revealed in the enzymatic environment. This study provided usefule insights into the underlying catalytic mechanism to contribute to disease-involved research.

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