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De novo design of protein structure and function with RFdiffusion.

Nature
There has been considerable recent progress in designing new proteins using deep-learning methods. Despite this progress, a general deep-learning framework for protein design that enables solution of a wide range of design challenges, including de no...

Machine Learning-Enhanced Quantum Chemistry-Assisted Refinement of the Active Site Structure of Metalloproteins.

Inorganic chemistry
Understanding the fine structural details of inhibitor binding at the active site of metalloenzymes can have a profound impact on the rational drug design targeted to this broad class of biomolecules. Structural techniques such as NMR, cryo-EM, and X...

Machine learning-based QSAR and LB-PaCS-MD guided design of SARS-CoV-2 main protease inhibitors.

Bioorganic & medicinal chemistry letters
The global outbreak of the COVID-19 pandemic caused by the SARS-CoV-2 virus had led to profound respiratory health implications. This study focused on designing organoselenium-based inhibitors targeting the SARS-CoV-2 main protease (M). The ligand-bi...

Int&in: A machine learning-based web server for active split site identification in inteins.

Protein science : a publication of the Protein Society
Inteins are proteins that excise themselves out of host proteins and ligate the flanking polypeptides in an auto-catalytic process called protein splicing. In nature, inteins are either contiguous or split. In the case of split inteins, the two fragm...

Multi-modal deep learning enables efficient and accurate annotation of enzymatic active sites.

Nature communications
Annotating active sites in enzymes is crucial for advancing multiple fields including drug discovery, disease research, enzyme engineering, and synthetic biology. Despite the development of numerous automated annotation algorithms, a significant trad...

Correlating enzymatic reactivity for different substrates using transferable data-driven collective variables.

Proceedings of the National Academy of Sciences of the United States of America
Machine learning (ML) is transforming the investigation of complex biological processes. In enzymatic catalysis, one significant challenge is identifying the reactive conformations (RC) of the enzyme:substrate complex where the substrate assumes a pr...

SCREEN: A Graph-based Contrastive Learning Tool to Infer Catalytic Residues and Assess Enzyme Mutations.

Genomics, proteomics & bioinformatics
The accurate identification of catalytic residues contributes to our understanding of enzyme functions in biological processes and pathways. The increasing number of protein sequences necessitates computational tools for the automated prediction of c...

Long-Range Electrostatics in Serine Proteases: Machine Learning-Driven Reaction Sampling Yields Insights for Enzyme Design.

Journal of chemical information and modeling
Computational enzyme design is a promising technique for producing novel enzymes for industrial and clinical needs. A key challenge that this technique faces is to consistently achieve the desired activity. Fundamental studies of natural enzymes reve...

Machine Learning-Guided Screening and Molecular Docking for Proposing Naturally Derived Drug Candidates Against MERS-CoV 3CL Protease.

International journal of molecular sciences
In this study, we utilized machine learning techniques to identify potential inhibitors of the MERS-CoV 3CL protease. Among the models evaluated, the Random Forest (RF) algorithm exhibited the highest predictive performance, achieving an accuracy of ...

Geometry-encoded molecular dynamics enables deep learning insights into P450 regiospecificity control.

Scientific reports
Cytochrome P450 1A2, as many isoenzymes, can generate multiple metabolites from a single substrate. A loose coupling between substrate binding and oxygen activation makes possible substrate reorientations at the active site prior to catalysis. In the...