Applicability of AlphaFold2 in the modelling of coiled-coil domains

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 10, 2024

Abstract Coiled coils are a common protein structural motif involved in cellular functions ranging from mediating protein-protein interactions to facilitating processes such as signal transduction or regulation of gene expression. They formed by two more alpha helices that wind around central axis form buried hydrophobic core. Various forms coiled-coil bundles have been reported, each characterized the number, orientation, and degree winding constituent helices. This variability is underpinned short sequence repeats coiled whose properties determine both their overall topology local geometry The strikingly repetitive has enabled development accurate sequence-based prediction methods; however, modeling domains remains challenging task. In this work, we evaluated accuracy AlphaFold2 domains, predicting global topological properties. Furthermore, show oligomeric state can be achieved using internal representations AlphaFold2, with performance better than any previous state-of-the-art method (code available at https://github.com/labstructbioinf/dc2_oligo ).

Язык: Английский

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Structure‐aware deep learning model for peptide toxicity prediction

Protein Science, Год журнала: 2024, Номер 33(7)

Опубликована: Июнь 22, 2024

Antimicrobial resistance is a critical public health concern, necessitating the exploration of alternative treatments. While antimicrobial peptides (AMPs) show promise, assessing their toxicity using traditional wet lab methods both time-consuming and costly. We introduce tAMPer, novel multi-modal deep learning model designed to predict peptide by integrating underlying amino acid sequence composition three-dimensional structure peptides. tAMPer adopts graph-based representation for peptides, encoding ColabFold-predicted structures, where nodes represent acids edges spatial interactions. Structural features are extracted graph neural networks, recurrent networks capture sequential dependencies. tAMPer's performance was assessed on publicly available protein benchmark an AMP hemolysis data we generated. On latter, achieves F1-score 68.7%, outperforming second-best method 23.4%. benchmark, exhibited improvement over 3.0% in compared current state-of-the-art methods. anticipate accelerate discovery development reducing reliance laborious screening experiments.

Язык: Английский

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Computational modeling and prediction of deletion mutants

Structure, Год журнала: 2023, Номер 31(6), С. 713 - 723.e3

Опубликована: Апрель 28, 2023

Язык: Английский

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DCTPep, the data of cancer therapy peptides

Scientific Data, Год журнала: 2024, Номер 11(1)

Опубликована: Май 25, 2024

Abstract With the discovery of therapeutic activity peptides, they have emerged as a promising class anti-cancer agents due to their specific targeting, low toxicity, and potential for high selectivity. In particular, peptide-drug conjugates enter clinical, coupling targeted peptides with traditional chemotherapy drugs or cytotoxic will become new direction in cancer treatment. To facilitate drug development therapy we constructed DCTPep, novel, open, comprehensive database peptides. addition anticancer (ACPs), peptide library also includes related therapy. These data were collected manually from published research articles, patents, other protein databases. Data on include clinically investigated and/or approved therapy, which mainly come portal websites regulatory authorities organisations different countries regions. DCTPep has total 6214 entries, believe that contribute design screening future

Язык: Английский

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Cell-permeable chameleonic peptides: Exploiting conformational dynamics in de novo cyclic peptide design

Current Opinion in Structural Biology, Год журнала: 2023, Номер 80, С. 102603 - 102603

Опубликована: Май 12, 2023

Membrane-traversing peptides offer opportunities for targeting intracellular proteins and oral delivery. Despite progress in understanding the mechanisms underlying membrane traversal natural cell-permeable peptides, there are still several challenges to designing membrane-traversing with diverse shapes sizes. Conformational flexibility appears be a key determinant of permeability large macrocycles. We review recent developments design validation chameleonic cyclic which can switch between alternative conformations enable improved through cell membranes, while maintaining reasonable solubility exposed polar functional groups target protein binding. Finally, we discuss principles, strategies, practical considerations rational design, discovery, permeable peptides.

Язык: Английский

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