The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(8), P. 950 - 959

Published: June 21, 2024

Language: Английский

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Can AlphaFold’s breakthrough in protein structure help decode the fundamental principles of adaptive cellular immunity?

Nature Methods, Journal Year: 2024, Volume and Issue: 21(5), P. 766 - 776

Published: April 23, 2024

Language: Английский

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MHC-Fine: Fine-tuned AlphaFold for precise MHC-peptide complex prediction

Biophysical Journal, Journal Year: 2024, Volume and Issue: 123(17), P. 2902 - 2909

Published: May 15, 2024

Language: Английский

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EnGens: a computational framework for generation and analysis of representative protein conformational ensembles

Briefings in Bioinformatics, Journal Year: 2023, Volume and Issue: 24(4)

Published: July 1, 2023

Proteins are dynamic macromolecules that perform vital functions in cells. A protein structure determines its function, but this is not static, as proteins change their conformation to achieve various functions. Understanding the conformational landscapes of essential understand mechanism action. Sets carefully chosen conformations can summarize such complex and provide better insights into function than single conformations. We refer these sets representative ensembles. Recent advances computational methods have led an increase number available structural datasets spanning landscapes. However, extracting ensembles from easy task many been developed tackle it. Our new approach, EnGens (short for ensemble generation), collects a unified framework generating analyzing In work, we: (1) overview existing tools generation analysis; (2) unify approaches open-source Python package, portable Docker image, providing interactive visualizations within Jupyter Notebook pipeline; (3) test our pipeline on few canonical examples literature. Representative produced by be used downstream tasks protein-ligand docking, Markov state modeling dynamics analysis effect single-point mutations.

Language: Английский

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Structural and physical features that distinguish tumor-controlling from inactive cancer neoepitopes

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(51)

Published: Dec. 12, 2023

Neoepitopes arising from amino acid substitutions due to single nucleotide polymorphisms are targets of T cell immune responses cancer and significant interest in the development vaccines. However, understanding characteristics rare protective neoepitopes that truly control tumor growth has been a challenge, their scarcity as well challenge verifying true, neoepitope-dependent humans. Taking advantage recent work mouse models circumvented these challenges, here, we compared structural physical properties range fully immunologically inactive. As derived self-peptides can induce tolerance, studied not only how various differ each other but also wild-type counterparts. We identified multiple features associated with protection, including describe self recognition by diverse receptor repertoires. demonstrate both promise limitations neoepitope analysis predictive modeling illustrate important aspects be incorporated into prediction pipelines.

Language: Английский

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Structural analyses of Cryptosporidium parvum epitopes reveal a novel scheme of decapeptide binding to H-2Kb

Journal of Structural Biology, Journal Year: 2025, Volume and Issue: 217(1), P. 108168 - 108168

Published: Jan. 13, 2025

Language: Английский

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Molecular docking to investigate HLA-associated idiosyncratic drug reactions

Drug Metabolism Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 34

Published: Jan. 15, 2025

Idiosyncratic drug reactions (IDRs) pose severe threats to patient health. Unlike conventionally dose-dependent side effects, they are unpredictable and more frequently manifest as life-threatening conditions, such cutaneous adverse (SCARs) drug-induced liver injury (DILI). Some HLA alleles, HLA-B*57:01, HLA-B*15:02, HLA-B*58:01, known risk factors for induced by multiple drugs. However, the structural basis underlying most HLA-associated events remains poorly understood. This review summarizes application of molecular docking reveal mechanisms IDR-related associations, covering studies using this technique examine drug-HLA binding pockets identify key residues. We provide a comprehensive overview alleles associated with IDRs, followed discussion utility limitations commonly used tools in simulating complex interactions within pocket. Through examples, including abacavir flucloxacillin carbamazepine allopurinol we demonstrate how analyses can insights into allele-specificity events. Furthermore, use screen drugs unknown IDR liability is examined, targeting either variants or single specific variant. Despite challenges, presents promising toolkit investigating understanding mechanisms, significant implications preemptive typing safer development.

Language: Английский

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AlphaFold and what is next: bridging functional, systems and structural biology

Expert Review of Proteomics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

The DeepMind's AlphaFold (AF) has revolutionized biomedical research by providing both experts and non-experts with an invaluable tool for predicting protein structures. However, while AF is highly effective structures of rigid globular proteins, it not able to fully capture the dynamics, conformational variability, interactions proteins ligands other biomacromolecules. In this review, we present a comprehensive overview latest advancements in 3D model predictions biomacromolecules using AF. We also provide detailed analysis its strengths limitations, explore more recent iterations, modifications, practical applications strategy. Moreover, map path forward expanding landscape toward every peptide proteome most physiologically relevant form. This discussion based on extensive literature search performed PubMed Google Scholar. While significant progress been made enhance AF's modeling capabilities, argue that combined approach integrating various silico vitro methods will be beneficial future structural biology, bridging gaps between static dynamic features their functions.

Language: Английский

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T-cell receptor structures and predictive models reveal comparable alpha and beta chain structural diversity despite differing genetic complexity

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 4, 2025

Language: Английский

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Cancer Immunogenomics Approaches and Applications to Cancer Vaccines

The Cancer Journal, Journal Year: 2025, Volume and Issue: 31(2)

Published: March 1, 2025

The application of next-generation sequencing–based genomics and corresponding analytical pipelines have significantly improved our ability to identify tumor-unique antigenic peptides (“neoantigens”) for the design personalized vaccine therapies monitor immune responses these vaccines. more recent implementation artificial intelligence machine learning into several complex components neoantigen selection process has provided significant improvements across a number previously difficult aspects within identification, as we will describe. Related technologies analytics been developed that enable characterization changes tumor microenvironment facilitated by vaccination systemic in patients. Here, review new methods their design, implementation, evaluation cancer

Language: Английский

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