Development of Parallel On-the-Fly Crystal Algorithm for Reaction Discovery in Large and Complex Molecular Systems

Journal of Chemical Theory and Computation, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

The parallel on-the-fly Crystal algorithm is a new, efficient global search for exploring single-state potential energy surfaces and conical intersection seam spaces of wide range molecules. Despite major developments, its application to complex molecular systems, especially in the condensed phase, remains challenging due high dimensionality configurational space. In this work, we address challenge extend applicability reaction discovery large photoswitches various environments, including phase with explicit solvent This achieved by performing an exploration comparatively subspace, while gradually relaxing remaining degrees freedom. new applied bilirubin donor-acceptor Stenhouse adducts, next-generation class photoswitches, vacuum aqueous solution. To end, designed automated systematic workflow discover characterize minima low-energy pathways these systems. Our findings demonstrate algorithm's effectiveness quickly configuration space uncovering kinetically accessible products, offering insights into intricate chemical reactivities molecules roles environments on pathways. results underscore promising parallelized methods biomolecular

Language: Английский

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Alternative Algebraic Perspectives on CO/H₂ PROX over MnO₂ Composite Catalysts

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

This study presents a graph-based approach to investigate the steady-state kinetics of preferential CO oxidation process in H2 (PROX) occurring on MnO2 model fragment with manganese centers at varying states, simulating surface Mn(IV) active sites composite MnO2-CeO2 catalyst previously used experimental applications. A novel modeling approach, termed DFT kinetic analysis (DFT-GKA), is introduced. It utilizes free activation energy (ΔG⧧) values characterize linear elementary events, supposed pseudosteady-state, this complex reaction system, as determined through density functional theory (DFT) integrated by thermochemical calculations. The implementation achieved using homemade Common Lisp code, specifically designed for efficient manipulation long lists essential analysis. Finally, comprehensive ab initio descriptors related CO/H2 PROX catalytic oxide fragments are discussed, highlighting their significance future research and

Language: Английский

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Characterizing Reaction Route Map of Realistic Molecular Reactions Based on Weight Rank Clique Filtration of Persistent Homology

Journal of Chemical Theory and Computation, Journal Year: 2023, Volume and Issue: 19(15), P. 5007 - 5023

Published: July 3, 2023

A reaction route map (RRM) constructed using the GRRM program is a collection of elementary pathways, each which comprises two equilibrium (EQ) geometries and one transition state (TS) geometry connected by an intrinsic coordinate (IRC). An RRM can be mathematically represented graph with weights assigned to both vertices, corresponding EQs, edges, TSs, representing energies. In this study, we propose method extract topological descriptors weighted based on persistent homology (PH). The work Mirth et al. [ J. Chem. Phys.2021, 154, 114114], in PH analysis was applied (3N - 6)-dimensional potential energy surface N atomic system, related present method, but our practically applicable realistic molecular reactions. Numerical assessments revealed that same information as proposed for 0-th 1-st PHs, except death PH. addition, obtained from corresponds disconnectivity graph. results study suggest accurately reflect characteristics chemical reactions and/or physicochemical properties system.

Language: Английский

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Exploring Chemical Space Using Ab Initio Hyperreactor Dynamics

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(2), P. 302 - 314

Published: Jan. 31, 2024

In recent years, first-principles exploration of chemical reaction space has provided valuable insights into intricate networks. Here, we introduce ab initio hyperreactor dynamics, which enables rapid screening the accessible from a given set initial molecular species, predicting new synthetic routes that can potentially guide subsequent experimental studies. For this purpose, different hyperdynamics derived bias potentials are applied along with pressure-inducing spherical confinement system in dynamics simulations to efficiently enhance reactivity under mild conditions. To showcase advantages and flexibility approach, present systematic study method's parameters on HCN toy model apply it recently introduced for prebiotic formation glycinal acetamide interstellar ices, yields results line findings. addition, show how developed framework complicated transitions like first step nonenzymatic DNA nucleoside synthesis an aqueous environment, where fragmentation problem earlier nanoreactor approaches is avoided.

Language: Английский

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Auto QSAR-based active learning docking for hit identification of potential inhibitors of Plasmodium falciparum Hsp90 as antimalarial agents

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(11), P. e0308969 - e0308969

Published: Nov. 25, 2024

Malaria which is mainly caused by Plasmodium falciparum parasite remains a devastating public health concern, necessitating the need to develop new antimalarial agents. P. heat shock protein 90 (Hsp90), indispensable for survival and promising drug target. Inhibitors targeting ATP-binding pocket of N-terminal domain have anti-Plasmodium effects. We proposed de novo active learning (AL) driven method in tandem with docking predict inhibitors unique scaffolds preferential selectivity towards PfHsp90. Reference compounds, predicted bind PfHsp90 at possessing activities, were used generate 10,000 derivatives build Auto-quantitative structures activity relationships (QSAR) models. Glide was performed scores > 15,000 compounds obtained from ChEMBL database. Re-iterative training testing models until optimum Kennel-based Partial Least Square (KPLS) regression model coefficient R2 = 0.75 set squared correlation prediction Q2 0.62 test reached convergence. Rescoring using induced fit molecular dynamics simulations enabled us prioritize 15 ATP/ADP-like design ideas purchase. The exerted moderate NF54 strain IC50 values ≤ 6μM displayed weak affinity (KD range: 13.5-19.9μM) comparable reported ADP. most potent compound FTN-T5 (PfN54 IC50:1.44μM; HepG2/CHO cells SI≥ 29) bound (KD:7.7μM), providing starting point optimization efforts. Our work demonstrates great utility AL rapid identification novel molecules discovery (i.e., hit identification). potency will be critical designing species-selective developing more efficient agents against malaria.

Language: Английский

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Auto QSAR-based Active learning docking for hit identification of potential inhibitors of Plasmodium falciparum Hsp90 as antimalarial agents

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 18, 2024

Abstract Malaria which is mainly caused by Plasmodium falciparum parasite remains a devastating public health concern, necessitating the need to develop new antimalarial agents. P. heat shock protein 90 (Hsp90), indispensable for survival and promising drug target. Inhibitors targeting ATP-binding pocket of N-terminal domain have anti- effects. We proposed de novo active learning (AL) driven method in tandem with docking predict inhibitors unique scaffolds preferential selectivity towards PfHsp90. Reference compounds, predicted bind PfHsp90 at possessing activities, were used generate 10,000 derivatives build Auto-quantitative structures activity relationships (QSAR) models. Glide was performed scores > 15,000 compounds obtained from ChEMBL database. Re-iterative training testing models until optimum Kennel-based Partial Least Square (KPLS) regression model coefficient R2 = 0.75 set squared correlation prediction Q2 0.62 test reached convergence. Rescoring using induced fit molecular dynamics simulations enabled us prioritize 15 ATP/ADP-like design ideas purchase. The exerted moderate NF54 strain IC 50 values ≤ 6μM displayed weak affinity (K D range: 13.5-19.9μM) comparable reported ADP. most potent compound FTN-T5 (PfN54 :1.44μM; HepG2/CHO cells SI≥ 29) bound :7.7μM), providing starting point optimization efforts. Our work demonstrates great utility AL rapid identification novel molecules discovery (i.e., hit identification). potency will be critical designing species-selective developing more efficient agents against malaria.

Language: Английский

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Modified Activation-Relaxation Technique (ARTn) Method Tuned for Efficient Identification of Transition States in Surface Reactions

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 6, 2024

Exploring potential energy surfaces (PES) is essential for unraveling the underlying mechanisms of chemical reactions and material properties. While activation-relaxation technique (ARTn) a state-of-the-art method identifying saddle points on PES, it often faces challenges in complex landscapes, especially surfaces. In this study, we introduce iso-ARTn, an enhanced ARTn that incorporates constraints orthogonal hyperplane employs adaptive active volume. By leveraging neural network (NNP) to conduct exhaustive point search Pt(111) surface with 0.3 monolayers oxygen coverage, iso-ARTn achieves success rate 8.2% higher than original ARTn, 40% fewer force calls. Moreover, effectively finds various without compromising rate. Combined kinetic Monte Carlo simulations event table construction, NNP demonstrates capability reveal structures consistent experimental observations. This work signifies substantial advancement investigation enhancing both efficiency breadth searches.

Language: Английский

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A knowledge-driven approach for automatic generation of reaction networks of methanol-to-olefins process

Chemical Engineering Science, Journal Year: 2023, Volume and Issue: 284, P. 119461 - 119461

Published: Nov. 3, 2023

Language: Английский

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Chemistry in a graph: modern insights into commercial organic synthesis planning

Digital Discovery, Journal Year: 2024, Volume and Issue: 3(9), P. 1682 - 1694

Published: Jan. 1, 2024

We present graph databases as a modern solution for storing and accessing chemical knowledge. This approach is demonstrated in commercial route selection holds the potential to create universal data-sharing framework chemistry.

Language: Английский

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Heron: Visualizing and Controlling Chemical Reaction Explorations and Networks

The Journal of Physical Chemistry A, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Automated and high-throughput quantum chemical investigations into processes have become feasible in great detail broad scope. This results an increase complexity of the tasks amount generated data. An efficient intuitive way for operator to interact with these data steer virtual experiments is required. Here, we introduce Heron, a graphical user interface that allows advanced human-machine interactions exploration campaigns molecular structure reactivity. Heron offers access interactive automated explorations reactions standard electronic modules, haptic force feedback, microkinetic modeling, refinement by correlated calculations including black-box complete active space calculations. It tailored analysis vast reaction networks. We show how interoperable modules enable workflows pave routine low-entrance-barrier modeling techniques.

Language: Английский

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