scholarly journals ChemSpaX: Exploration of Chemical Space by Automated Functionalization of Molecular Scaffold

2021 ◽  
Author(s):  
Adarsh Kalikadien ◽  
Evgeny A. Pidko ◽  
Vivek Sinha
Keyword(s):  
Transition Metal ◽  
Chemical Space ◽  
Data Driven ◽  
Molecular Scaffolds ◽  
Molecular Scaffold ◽  
Automated Generation ◽  
Design And Optimization ◽  
Screening Design ◽  
Computational Screening ◽  
And Function

Exploration of the local chemical space of molecular scaffolds by post-functionalization (PF) is a promising route to discover novel molecules with desired structure and function. PF with rationally chosen substituents based on known electronic and steric properties is a commonly used experimental and computational strategy in screening, design and optimization of catalytic scaffolds. Automated generation of reasonably accurate geometric representations of post-functionalized molecular scaffolds is highly desirable for data-driven applications. However, automated PF of transition metal (TM) complexes remains challenging. In this work a Python-based workflow, ChemSpaX, that is aimed at automating the PF of a given molecular scaffold with special emphasis on TMcomplexes, is introduced. In three representative applications of ChemSpaX by comparing with DFT and DFT-B calculations, we show that the generated structures have a reasonable quality for use in computational screening applications. Furthermore, we show thatChemSpaXgenerated geometries can be used in machine learning applications to accurately predict DFT computed HOMO-LUMO gaps for transition metal complexes.ChemSpaXis open-source and aims to bolster and democratize the efforts of the scientific community towards data-driven chemical discovery.

scholarly journals ChemSpaX: Exploration of chemical space by automated functionalization of molecular scaffold

2022 ◽  
Author(s):  
Adarsh V. Kalikadien ◽  
Evgeny A Pidko ◽  
Vivek Sinha
Keyword(s):  
Chemical Space ◽  
Structure And Function ◽  
Molecular Scaffolds ◽  
Molecular Scaffold ◽  
And Function ◽  
Post Functionalization

Exploration of the local chemical space of molecular scaffolds by post-functionalization (PF) is a promising route to discover novel molecules with desired structure and function. PF with rationally chosen substituents...

scholarly journals Chemical Space Mapping for Multicomponent Gas Mixtures

2021 ◽  
Author(s):  
Airat Kotliar-Shapirov ◽  
Fedor S. Fedorov ◽  
Henni Ouerdane ◽  
Stanislav Evlashin ◽  
Albert G. Nasibulin ◽  
...  
Keyword(s):  
Cyclic Voltammetry ◽  
Data Processing ◽  
Electrochemical Sensors ◽  
Chemical Space ◽  
Chemical Species ◽  
Single Species ◽  
Data Driven ◽  
Multicomponent Gas ◽  
Data Driven Approach ◽  
Cyclic Voltammetry Data

In our manuscript, we present our protocol for data processing to mitigate the effects of interfering analytes on the identification of the chemical species detected by sensors. Considering NO2 and CO2, we designed electrochemical sensors whose response yielded the cyclic voltammetry data that we analyzed to classify single-species components and their mixtures using a data-driven approach to generate a chemical space where their mixtures can be deconvoluted.<br>

scholarly journals ChemSpaX: Exploration of Chemical Space by Automated Functionalization of Molecular Scaffold

2021 ◽  
Author(s):  
Adarsh Kalikadien ◽  
Evgeny A. Pidko ◽  
Vivek Sinha
Keyword(s):  
Force Field ◽  
High Throughput ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Space Exploration ◽  
Molecular Structures ◽  
Data Driven ◽  
Pincer Complexes ◽  
Cobalt Porphyrin ◽  
Input Structure

<div>Local chemical space exploration of an experimentally synthesized material can be done by making slight structural</div><div>variations of the synthesized material. This generation of many molecular structures with reasonable quality,</div><div>that resemble an existing (chemical) purposeful material, is needed for high-throughput screening purposes in</div><div>material design. Large databases of geometry and chemical properties of transition metal complexes are not</div><div>readily available, although these complexes are widely used in homogeneous catalysis. A Python-based workflow,</div><div>ChemSpaX, that is aimed at automating local chemical space exploration for any type of molecule, is introduced.</div><div>The overall computational workflow of ChemSpaX is explained in more detail. ChemSpaX uses 3D information,</div><div>to place functional groups on an input structure. For example, the input structure can be a catalyst for which one</div><div>wants to use high-throughput screening to investigate if the catalytic activity can be improved. The newly placed</div><div>substituents are optimized using a computationally cheap force-field optimization method. After placement of</div><div>new substituents, higher level optimizations using xTB or DFT instead of force-field optimization are also possible</div><div>in the current workflow. In representative applications of ChemSpaX, it is shown that the structures generated by</div><div>ChemSpaX have a reasonable quality for usage in high-throughput screening applications. Representative applications</div><div>of ChemSpaX are shown by investigating various adducts on functionalized Mn-based pincer complexes,</div><div>hydrogenation of Ru-based pincer complexes, functionalization of cobalt porphyrin complexes and functionalization</div><div>of a bipyridyl functionalized cobalt-porphyrin trapped in a M2L4 type cage complex. Descriptors such as</div><div>the Gibbs free energy of reaction and HOMO-LUMO gap, that can be used in data-driven design and discovery</div><div>of catalysts, were selected and studied in more detail for the selected use cases. The relatively fast GFN2-xTB</div><div>method was used to calculate these descriptors and a comparison was done against DFT calculated descriptors.</div><div>ChemSpaX is open-source and aims to bolster the efforts of the scientific community towards data-driven material</div><div>discovery.</div>

scholarly journals Computational High-Throughput Screening of Polymeric Photocatalysts: Exploring the Effect of Composition, Sequence Isomerism and Conformational Degrees of Freedom

2018 ◽  
Author(s):  
isabelle Heath-Apostolopoulos ◽  
Liam Wilbraham ◽  
Martijn Zwijnenburg
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Degrees Of Freedom ◽  
Chemical Space ◽  
Low Cost ◽  
Computational Screening ◽  
Computational Workflow ◽  
Conformational Degrees Of Freedom

We discuss a low-cost computational workflow for the high-throughput screening of polymeric photocatalysts and demonstrate its utility by applying it to a number of challenging problems that would be difficult to tackle otherwise. Specifically we show how having access to a low-cost method allows one to screen a vast chemical space, as well as to probe the effects of conformational degrees of freedom and sequence isomerism. Finally, we discuss both the opportunities of computational screening in the search for polymer photocatalysts, as well as the biggest challenges.

scholarly journals Coordinating ERK signaling via the molecular scaffold Kinase Suppressor of Ras

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1621 ◽  
Author(s):  
Danielle Frodyma ◽  
Beth Neilsen ◽  
Diane Costanzo-Garvey ◽  
Kurt Fisher ◽  
Robert Lewis
Keyword(s):  
Energy Balance ◽  
Small Molecule ◽  
Physiological Role ◽  
Molecular Scaffolds ◽  
Potent Effect ◽  
Molecular Scaffold ◽  
Kinase Suppressor Of Ras ◽  
Kinase Cascade ◽  
Reduced Toxicity ◽  
Erk Kinase

Many cancers, including those of the colon, lung, and pancreas, depend upon the signaling pathways induced by mutated and constitutively active Ras. The molecular scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade. Here we summarize the canonical role of KSR in cells, including its central role as a scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of various cellular pathways mediated through different binding partners, and the phenotypic consequences of KSR1 or KSR2 genetic inactivation. Mammalian KSR proteins have a demonstrated role in cellular and organismal energy balance with implications for cancer and obesity. Targeting KSR1 in cancer using small molecule inhibitors has potential for therapy with reduced toxicity to the patient. RNAi and small molecule screens using KSR1 as a reference standard have the potential to expose and target vulnerabilities in cancer. Interestingly, although KSR1 and KSR2 are similar in structure, KSR2 has a distinct physiological role in regulating energy balance. Although KSR proteins have been studied for two decades, additional analysis is required to elucidate both the regulation of these molecular scaffolds and their potent effect on the spatial and temporal control of ERK activation in health and disease.

scholarly journals Molecular Communications: Model-Based and Data-Driven Receiver Design and Optimization

IEEE Access ◽  
2019 ◽  
Vol 7 ◽  
pp. 53555-53565 ◽  
Author(s):  
Xuewen Qian ◽  
Marco Di Renzo ◽  
Andrew Eckford
Keyword(s):  
Data Driven ◽  
Receiver Design ◽  
Design And Optimization ◽  
Model Based

Retaining Alkyl Nucleophile Regiofidelity in Transition-Metal-Mediated Cross-Couplings to Aryl Electrophiles

Synthesis ◽  
2018 ◽  
Vol 50 (20) ◽  
pp. 3974-3996 ◽  
Author(s):  
Josep Cornella ◽  
Matthew O’Neill
Keyword(s):  
Transition Metal ◽  
Functional Group ◽  
Chemical Space ◽  
Cross Coupling ◽  
Transition Metal Catalysis ◽  
Metal Catalysis ◽  
Substantial Progress ◽  
Tertiary Alkyl ◽  
Metal Ligand

While the advent of transition-metal catalysis has undoubtedly transformed synthetic chemistry, problems persist with the introduction of secondary and tertiary alkyl nucleophiles into C(sp2) aryl electrophiles. Complications arise from the delicate organometallic intermediates typically invoked by such processes, from which competition between the desired reductive elimination event and the deleterious β-H elimination pathways can lead to undesired isomerization of the incoming nucleophile. Several methods have integrated distinct combinations of metal, ligand, nucleophile, and electrophile to provide solutions to this problem. Despite substantial progress, refinements to current protocols will facilitate the realization of complement reactivity and improved functional group tolerance. These issues have become more pronounced in the context of green chemistry and sustainable catalysis, as well as by the current necessity to develop robust, reliable cross-couplings beyond less explored C(sp2)–C(sp2) constructs. Indeed, the methods discussed herein and the elaborations thereof enable an ‘unlocking’ of accessible topologically enriched chemical space, which is envisioned to influence various domains of application.1 Introduction2 Mechanistic Considerations3 Magnesium Nucleophiles4 Zinc Nucleophiles5 Boron Nucleophiles6 Other Nucleophiles7 Tertiary Nucleophiles8 Reductive Cross-Coupling with in situ Organometallic Formation9 Conclusion

scholarly journals ScaffoldGraph: an open-source library for the generation and analysis of molecular scaffold networks and scaffold trees

2020 ◽  
Vol 36 (12) ◽  
pp. 3930-3931 ◽  
Author(s):  
Oliver B Scott ◽  
A W Edith Chan
Keyword(s):  
Open Source ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Diversity Analysis ◽  
Graph Analysis ◽  
Command Line ◽  
Molecular Scaffold ◽  
Large Sets ◽  
Command Line Tool ◽  
Scaffold Diversity

Abstract Summary ScaffoldGraph (SG) is an open-source Python library and command-line tool for the generation and analysis of molecular scaffold networks and trees, with the capability of processing large sets of input molecules. With the increase in high-throughput screening data, scaffold graphs have proven useful for the navigation and analysis of chemical space, being used for visualization, clustering, scaffold-diversity analysis and active-series identification. Built on RDKit and NetworkX, SG integrates scaffold graph analysis into the growing scientific/cheminformatics Python stack, increasing the flexibility and extendibility of the tool compared to existing software. Availability and implementation SG is freely available and released under the MIT licence at https://github.com/UCLCheminformatics/ScaffoldGraph.

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