Unraveling Protein–Protein Interactions for Innovative Therapeutics and Nanodelivery

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Biophysics".

Deadline for manuscript submissions: 20 October 2025 | Viewed by 364

Special Issue Editors


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Guest Editor
IC—Consiglio Nazionale delle Ricerche, Rome, Italy
Interests: structural biology; molecular mechanisms; bioinformatics

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Guest Editor
SCITEC—Consiglio Nazionale delle Ricerche, Rome, Italy
Interests: bioactive peptides; protein–protein events modulation; nanodelivery
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Special Issue Information

Dear Colleagues,

Protein–protein interactions (PPIs) are fundamental to all biological processes, playing crucial roles in cellular signaling, immune responses, and metabolic pathways. The intricate network of PPIs governs the functionality of cells, and their dysregulation is often implicated in various diseases, including cancer, neurodegenerative disorders, and infectious diseases. As our understanding of the molecular mechanisms underlying these interactions deepens, targeting PPIs for therapeutic intervention has emerged as a promising frontier in drug discovery.

Recent advancements in high-throughput screening techniques, structural biology, and computational modeling have significantly enhanced our ability to identify and characterize PPIs. These tools allow researchers to elucidate the dynamic nature of protein interactions and to explore the conformational changes that occur during binding events. Importantly, the development of small molecules, peptides, and biologics that can selectively disrupt or stabilize specific PPIs offers a novel approach to modulate biological pathways and restore homeostasis in diseased states. This Special Issue aims to highlight the latest research and innovative strategies in the field of PPI-targeted therapies.

We welcome contributions that explore various aspects of PPIs, including their role in disease mechanisms, methodologies for PPI identification and validation, and the design of therapeutic agents aimed at modulating these interactions. By bringing together diverse perspectives and innovative findings, we hope to foster a deeper understanding of the therapeutic potential of targeting protein–protein interactions and to inspire future research directions in this exciting area of biomedical science.

Dr. Roberta Montanari
Dr. Alberto Vitali
Guest Editors

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Keywords

  • protein–protein interactions
  • PPI modulators
  • nanodelivery
  • molecular mechanisms

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Published Papers (1 paper)

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Review

31 pages, 3629 KB  
Review
Sequence-Based Protein–Protein Interaction Prediction and Its Applications in Drug Discovery
by François Charih, James R. Green and Kyle K. Biggar
Cells 2025, 14(18), 1449; https://doi.org/10.3390/cells14181449 - 16 Sep 2025
Viewed by 215
Abstract
Aberrant protein–protein interactions (PPIs) underpin a plethora of human diseases, and disruption of these harmful interactions constitute a compelling treatment avenue. Advances in computational approaches to PPI prediction have closely followed progress in deep learning and natural language processing. In this review, we [...] Read more.
Aberrant protein–protein interactions (PPIs) underpin a plethora of human diseases, and disruption of these harmful interactions constitute a compelling treatment avenue. Advances in computational approaches to PPI prediction have closely followed progress in deep learning and natural language processing. In this review, we outline the state-of-the-art methods for sequence-based PPI prediction and explore their impact on target identification and drug discovery. We begin with an overview of commonly used training data sources and techniques used to curate these data to enhance the quality of the training set. Subsequently, we survey various PPI predictor types, including traditional similarity-based approaches, and deep learning-based approaches with a particular emphasis on transformer architecture. Finally, we provide examples of PPI prediction in system-level proteomics analyses, target identification, and designs of therapeutic peptides and antibodies. This review sheds light on sequence-based PPI prediction, a broadly applicable alternative to structure-based methods, from a unique perspective that emphasizes their roles in the drug discovery process and rigorous model assessment. Full article
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