Anticancer Effects of Pleurotus salmoneostramineus Protein Hydrolysate on HepG2 Cells and In Silico Characterization of Structural Effects of Chromoprotein-Derived Peptides on the Mitochondrial Uncoupling Protein 2 (UCP2)
Abstract
:1. Introduction
2. Materials and Methods
2.1. In Silico Cromoprotein Hydrolysis and Peptide Characterization
2.2. Prediction of Anticancer Potential of Peptides
2.3. Prediction of Peptide–Protein Interactions and Molecular Docking
2.4. Molecular Dynamics of Peptide–UCP2 Complexes
2.5. Preparation of the Protein Hydrolysate from P. salmoneostramineus (PSPs)
2.6. Cell Culture
2.7. Oxygen Consumption Rate (OCR)
2.8. Protein Quantification Assay
2.9. Statistical Analysis
3. Results
3.1. Pink Chromoprotein Hydrolysis and Peptide Physiochemical Parameters
3.2. Peptide Therapeutic Bioactivity and Anticancer Potential
3.3. Prediction of the GDP Binding Site in UCP2 Structure
3.4. Peptide Affinity for UCP2 and Molecular Docking
3.5. Peptide Translocation Mechanism Through UCP2
3.6. Molecular Dynamics Simulations for Peptide–UCP2 Complexes
3.7. Effect of PSPs on Uncoupling Activity in HepG2 Cells
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ANT2 | Adenine nucleotide translocator 2 |
BPs | Bioactive peptides |
HCC | Hepatocellular carcinoma |
MD | Molecular dynamics |
MTPs | Mitochondria-targeted peptides |
PCP | Pink chromoprotein |
RG | Radius of gyration |
RMSD | Root Mean Square Deviation |
RMSF | Root Mean Square Fluctuations |
SASA | Solvent-Accessible Surface Area |
SLC25s | Mitochondrial solute carriers |
THPs | Tumor-homing peptides |
UCP2 | Uncoupling protein 2 |
PSPs | Protein hydrolysate from P. salmoneostramineus |
References
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Peptide Sequence | Mass (g/mol) | Position (Res. Number) | Hydrophilicity | Peptide Ranker | Half-Life (sec) |
---|---|---|---|---|---|
SQTTKESPSA | 1035.49 | 59–68 | 0.5 | 0.055 | 1.634 |
PQEDKSA | 774.36 | 37–43 | 1.29 | 0.083 | 1.672 |
TSMQSSL | 753.34 | 164–170 | −0.34 | 0.149 | 1.378 |
TSQESY | 714.29 | 49–54 | 0.18 | 0.061 | 2.148 |
QEGQKL | 702.37 | 129–134 | 0.77 | 0.184 | 2.616 |
SEDSGEA | 694.25 | 194–200 | 1.3 | 0.092 | 2.810 |
PGSHPV | 593.30 | 140–145 | −0.28 | 0.382 | 2.581 |
GRNSL | 546.29 | 19–23 | 0.34 | 0.304 | 1.284 |
Peptide Sequence | Activity Prediction | |||||
---|---|---|---|---|---|---|
AAP | ABP | ACP | AIP | AVP | QSP | |
SQTTKESPSA | 0.52 | --------- | ------- | ------- | --------- | -------- |
PQEDKSA | 0.56 | --------- | ------- | -------- | --------- | -------- |
TSMQSSL | ---------- | --------- | 0.65 | 0.55 | --------- | 0.93 |
TSQESY | ---------- | --------- | ------- | 0.99 | --------- | 0.55 |
QEGQKL | ---------- | --------- | 0.79 | 0.64 | --------- | 0.51 |
SEDSGEA | 0.50 | --------- | 0.53 | ------- | --------- | ------- |
PGSHPV | 0.54 | --------- | ------- | ------- | --------- | 0.96 |
GRNSL | 0.56 | --------- | 0.56 | ------- | --------- | 1.00 |
Peptide Sequence | Multiple Peptide Servers | ||||||
---|---|---|---|---|---|---|---|
SCMTHP | mACPpred | TumorHPD | PreTP-Stack | TriNet | AntiCP 2.0 | CAPTURE | |
SQTTKESPSA | NON-THP (257.8) | ACP (0.529) | NON-THP (−0.33) | ACP (0.5) | 0.0 | AntiCP (0.49) | prostate |
PQEDKSA | NON-THP (223.8) | ACP (0.551) | NON-THP (−1.94) | ACP (0.5) | 0.0 | AntiCP (0.45) | colon |
TSMQSSL | THP (315.5) | ACP (0.655) | THP (0.81) | ACP (0.5) | 0.0 | Non-AntiCP (0.38) | colon |
TSQESY | NON-THP (250.3) | ACP (0.587) | NON-THP (−0.38) | ACP (0.5) | 0.0 | AntiCP (0.53) | skin |
QEGQKL | NON-THP (173.1) | ACP (0.722) | NON-THP (−0.99) | ACP (0.5) | 0.0 | AntiCP (0.7) | skin |
SEDSGEA | NON-THP (195.4) | ACP (0.575) | NON-THP (−1.35) | ACP (0.5) | 0.0 | Non-AntiCP (0.21) | breast |
PGSHPV | THP (361.3) | ACP (0.817) | THP (0.86) | ACP (0.7) | 1.0 | AntiCP (0.69) | colon |
GRNSL | THP (346.2) | ACP (0.789) | THP (0.94) | ACP (0.5) | 0.0 | AntiCP (0.5) | colon |
Peptide Sequence | PepSite2 p-Value | ITScorePeP | HPEPDOCK 2.0 |
---|---|---|---|
SQTTKESPSA | 0.02 | −116.4 | −156.04 |
PQEDKSA | 0.09 | −102.0 | −137.38 |
TSMQSSL | 0.05 | −102.9 | −166.75 |
TSQESY | 0.03 | −108.4 | −148.36 |
QEGQKL | 0.02 | −101.8 | −126.06 |
SEDSGEA | 0.16 | −83.0 | −99.93 |
PGSHPV | 0.02 | −89.0 | −164.64 |
GRNSL | 0.04 | −82.8 | −137.93 |
Parameters | Control (pmol/min/Protein O.D) | Genipin (30 µM) | PSPs (150 µg/mL) |
---|---|---|---|
Basal | 133.66 ± 3.57 | 115.6 ± 2.1 * | 111.3 ± 1.52 * |
ATP-linked Resp | 95.7 ± 4.8 | 96.2 ± 1.5 | 106.8 ± 3.2 * |
Proton Leak (UCP) | 33.7 ± 4.9 | 2.9 ± 3.73 ** | 2.56 ± 0.4 ** |
Max Resp | 243.25 ± 3.6 | 196.25 ± 6.75 ** | 180.8 ± 4.1 ** |
SRC | 102.5 ± 3.8 | 81.25 ± 6.9 ** | 56.17 ± 3.6 ** |
Non-Mito Resp | 8.65 ± 0.4 | 21.6 ± 3.5 ** | 18.52 ± 0.8 ** |
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Ventura-García, E.K.; Valdez-Solana, M.A.; Avitia-Domínguez, C.; García-Arenas, G.; Téllez-Valencia, A.; Balagurusamy, N.; Sierra-Campos, E. Anticancer Effects of Pleurotus salmoneostramineus Protein Hydrolysate on HepG2 Cells and In Silico Characterization of Structural Effects of Chromoprotein-Derived Peptides on the Mitochondrial Uncoupling Protein 2 (UCP2). BioMedInformatics 2025, 5, 29. https://doi.org/10.3390/biomedinformatics5020029
Ventura-García EK, Valdez-Solana MA, Avitia-Domínguez C, García-Arenas G, Téllez-Valencia A, Balagurusamy N, Sierra-Campos E. Anticancer Effects of Pleurotus salmoneostramineus Protein Hydrolysate on HepG2 Cells and In Silico Characterization of Structural Effects of Chromoprotein-Derived Peptides on the Mitochondrial Uncoupling Protein 2 (UCP2). BioMedInformatics. 2025; 5(2):29. https://doi.org/10.3390/biomedinformatics5020029
Chicago/Turabian StyleVentura-García, Erica K., Mónica A. Valdez-Solana, Claudia Avitia-Domínguez, Guadalupe García-Arenas, Alfredo Téllez-Valencia, Nagamani Balagurusamy, and Erick Sierra-Campos. 2025. "Anticancer Effects of Pleurotus salmoneostramineus Protein Hydrolysate on HepG2 Cells and In Silico Characterization of Structural Effects of Chromoprotein-Derived Peptides on the Mitochondrial Uncoupling Protein 2 (UCP2)" BioMedInformatics 5, no. 2: 29. https://doi.org/10.3390/biomedinformatics5020029
APA StyleVentura-García, E. K., Valdez-Solana, M. A., Avitia-Domínguez, C., García-Arenas, G., Téllez-Valencia, A., Balagurusamy, N., & Sierra-Campos, E. (2025). Anticancer Effects of Pleurotus salmoneostramineus Protein Hydrolysate on HepG2 Cells and In Silico Characterization of Structural Effects of Chromoprotein-Derived Peptides on the Mitochondrial Uncoupling Protein 2 (UCP2). BioMedInformatics, 5(2), 29. https://doi.org/10.3390/biomedinformatics5020029