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Published on: November 21, 2023
Exploring Placental Protein-Target Protein Interactions: In Silico and In Vitro Approaches for Osteoarthritis Therapy
Jithu Jerin James1, K V Sandhya1, Parasuraman Pavadai2
1Department of Pharmaceutics, Faculty of Pharmacy, MS Ramaiah University of Applied Sciences, Bengaluru, India.
Background:
Osteoarthritis (OA) is a persistent joint condition marked by gradual softening and breakdown of articular cartilage. Current research in OA treatment explores biologics that target proinflammatory cytokines and proteases, as well as promote chondrocyte regeneration and cartilage repair. Human placental tissues, abundant in anti-catabolic factors, can mitigate cartilage degradation by inhibiting protease expression and maintaining cartilage homeostasis in the presence of anabolic factors.
Objective:
This investigation examined placental protein interactions with proteases and OA target proteins through protein-protein docking and dynamic studies.
Methods:
The NCBI conserved domain database was utilized to predict functional protein domains. Protein sequence motifs were identified using literature, the MEME suite tool, and the My- Hits database. The Expasy-ProtParam online tool was employed to analyze protein physical parameters. ClusPro Advanced Options was used to dock binding site residues of selected placental proteins against specific OA target proteins, while PDBsum and Biovia Discovery Studio were used to visualize and examine molecular interactions. A 100 ns molecular dynamics (MD) study was conducted using DESMOND software.
Results:
Protein-protein docking revealed strong interactions of placental proteins with docking scores ranging from -1700 to -2450.3 against proteases and -900 to -1400 against specific target proteins. PDBsum analysis of placental protein-target protein docked complexes revealed residue interactions, hydrogen bonds, and non-bonded contacts. Molecular dynamics simulations further confirmed the stability of these complexes, indicating favorable protein-protein interactions (PPIs). The anti-inflammatory activity of human placental tissue against lipopolysaccharide-induced macrophages was investigated using flow cytometry.
Conclusion:
These results provide a foundation for future experimental studies to confirm the predicted interactions and to explore their potential therapeutic applications in OA treatment. Additionally, patients with OA and other arthritic conditions could benefit from the biologics chondroprotective biofactors, which serve as a promising alternative to conventional knee replacement surgery.
Insights
Human placental proteins show strong interactions with osteoarthritis targets, suggesting potential as a biologic therapy for cartilage repair and a promising alternative to knee replacement surgery.
Area of Science:
- Biochemistry and Molecular Biology
- Biomaterials Science
- Computational Biology
Background:
- Osteoarthritis (OA) involves articular cartilage degradation, prompting research into biologics for chondrocyte regeneration and cartilage repair.
- Human placental tissues contain anti-catabolic factors that can inhibit protease activity and maintain cartilage homeostasis.
Purpose of the Study:
- To investigate placental protein interactions with osteoarthritis (OA) target proteins using computational methods.
- To analyze protein-protein docking and molecular dynamics of these interactions.
Main Methods:
- Protein functional domains predicted using NCBI conserved domain database.
- Protein motifs identified via literature, MEME suite, and My-Hits.
- Physical parameters analyzed with Expasy-ProtParam.
- Protein-protein docking performed using ClusPro; interactions visualized with PDBsum and Biovia Discovery Studio.
- Molecular dynamics simulations conducted using DESMOND software.
Main Results:
- Strong protein-protein docking interactions observed between placental proteins and OA targets (scores -1700 to -2450.3).
- Analysis revealed specific residue interactions, hydrogen bonds, and non-bonded contacts in docked complexes.
- Molecular dynamics simulations confirmed the stability and favorable nature of these protein-protein interactions (PPIs).
Conclusions:
- Findings support future experimental validation of predicted placental protein-OA target interactions.
- These interactions hold potential for therapeutic applications in osteoarthritis treatment.
- Placental biofactors offer a promising alternative to conventional treatments like knee replacement surgery.
