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Innovative Approaches for Investigations on Protein Interactions

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 September 2025 | Viewed by 1179

Special Issue Editors


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Guest Editor
Department of Medicine and Surgery, University of Salerno, Salerno, Italy
Interests: drug target identification; protein–drug interaction; bioanalytical mass spectrometry; pharmacokinetics; proteomics; bioactive natural compounds
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Guest Editor Assistant
Department of Medicine and Surgery, Università degli Studi di Salerno, Salerno, Italy
Interests: proteins; outer membrane vesicles; drug delivery; protein engineering; structural biology; antioxidants; natural compounds; bioremediation; mass spectrometry; targeted drug monitoring; biomarkers

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Guest Editor Assistant
Department of Medicine and Surgery, Università degli Studi di Salerno, Salerno, Italy
Interests: proteomics; drug discovery; target identification; mass spectrometry; proteins-proteins interaction; proteins-molecule interaction; cell culture; 3D cell model

Special Issue Information

Dear Colleagues,

Proteins are key cellular components. Their wide variety and the plasticity of their structure–function paradigm make them essential in all biological functions in cells. Indeed, the biological effects of bioactive molecules are often a consequence of protein–protein (PP) or protein–ligand (PL) interactions.

Unravelling the complexity of PP and PL interactions is also vital for the development of biotechnological applications for exploiting these interactions. In recent years, key protein regulators have been identified as lead macromolecules engineered for optimizing drug delivery and as potential targets of drugs and therapeutics. Moreover, PP and PL interaction studies are essential for assessing the interactomic profiles of proteins in response to bioactive molecules, as well as for elucidating drugs action mechanism. Observing variations in the interactomic profiles of defined proteins or pathways is also a promising means of biomarker discovery, allowing us to characterize pathological proteomic patterns in biological matrixes.

Protein interactions can be investigated through different biochemical techniques, ranging from cell-free to cell-based assays. These different experimental settings could be used in combination with mass-spectrometry (MS)-based or immunometric detection methods. The use of antibodies for immune-capturing strategies (IP and co-IP) is an invaluable tool for investigating proteins’ interactomes. However, MS-based proteomic techniques are very attractive methods, as they allow for the simultaneous determination of multiple proteins and their targets. Moreover, different MS-based applications have emerged that are specifically designed to investigate the interactions between proteins and specific ligands; some examples include the DARTS assay, LiP assay and CETSA assay, specifically exploiting variations in proteins’ sensitivity to proteases or their thermal stabilization in the presence of ligand binding. Each of these strategies present advantages and drawbacks, including the limitations of targeted analysis in some cases and the risk of off-target identification. Therefore, we recommend validating interaction data by using an orthogonal technique.

In conclusion, many methodological approaches are available that investigate the landscape of PP and PL interactions. These techniques allow us to shed light on metabolic pathways, identify promising biomarkers, and unravel the action mechanisms of drugs and bioactive molecules, aiding drug development and drug discovery from early stages to target validation. This Special issue will include original research and review articles concerning innovative applications and advances in current strategies for the investigation of protein–protein and protein–drug interactions in all the cited fields of interest.

Dr. Fabrizio Dal Piaz
Guest Editor

Dr. Francesca Mensitieri
Dr. Maria Laura Bellone
Guest Editor Assitants

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Keywords

  • protein–protein and protein–ligand interactions
  • proteomics
  • innovative approaches
  • LC-MS/MS
  • immunometric techniques
  • interactome
  • drug discovery and development

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Published Papers (1 paper)

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Research

14 pages, 1156 KiB  
Article
Predicting Motif-Mediated Interactions Based on Viral Genomic Composition
by Sobia Idrees, Keshav Raj Paudel, Mithila Banik, Newton Suwal, Rajan Thapa and Saroj Bashyal
Int. J. Mol. Sci. 2025, 26(8), 3674; https://doi.org/10.3390/ijms26083674 - 13 Apr 2025
Viewed by 894
Abstract
Viruses manipulate host cellular machinery to propagate their life cycle, with one key strategy being the mimicry of short linear motifs (SLiMs) found in host proteins. While databases continue to expand with virus–host protein–protein interaction (vhPPI) data, accurately predicting viral mimicry remains challenging [...] Read more.
Viruses manipulate host cellular machinery to propagate their life cycle, with one key strategy being the mimicry of short linear motifs (SLiMs) found in host proteins. While databases continue to expand with virus–host protein–protein interaction (vhPPI) data, accurately predicting viral mimicry remains challenging due to the inherent degeneracy of SLiMs. In this study, we investigate how viral genomic composition influences motif mimicry and the mechanisms through which viruses hijack host cellular functions. We assessed domain–motif interaction (DMI) enrichment differences, and also predicted new DMIs based on known viral motifs with varying stringency levels, using SLiMEnrich v.1.5.1. Our findings reveal that dsDNA viruses capture significantly more known DMIs compared to other viral groups, with dsRNA viruses also exhibiting higher DMI enrichment than ssRNA viruses. Additionally, we identified new vhPPIs mediated via SLiMs, particularly within different viral genomic contexts. Understanding these interactions is vital for elucidating viral strategies to hijack host functions, which could inform the development of targeted antiviral therapies. Full article
(This article belongs to the Special Issue Innovative Approaches for Investigations on Protein Interactions)
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