Antihypertensive and Antidiabetic Drug Candidates from Milkfish (Chanos chanos)—Identification and Characterization through an Integrated Bioinformatic Approach
Abstract
:1. Introduction
2. Materials and Methods
2.1. Protein Extraction and Profiling of Milkfish Muscle Tissue
2.2. Protein Sequence Selection from the Database
2.3. Identification of Protein Physicochemical Properties and Amino Acid Distribution
2.4. In Silico Proteolysis and Peptide Profiling
2.5. Novel Peptides’ Bioactivities
2.6. Peptide Structure Modeling and Docking
3. Results
3.1. Protein Profiling and Identification
3.2. Protein Physicochemical Properties and Amino Acid Distribution
3.3. Peptide Frequency
3.4. Profiling of Bioactive Peptides
3.5. Novel Peptide Bioactivity Screening
3.6. Molecular Docking Analysis
3.7. ACE-Inhibitor Molecular Interaction
3.8. DPPIV-Inhibitor Molecular Interaction
3.9. Drug-Likeness Analysis
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Protein | a −R (Asp + Glu) | b +R (Arg + Lys) | Instability Index | Aliphatic Index | c GRAVY | Molecular Weight (Da) | Accession ID |
---|---|---|---|---|---|---|---|
Myosin heavy chain | 277 | 47 | 44.15 | 81.96 | −0.646 | 182,253.3 | A0A6J2VD67 |
Collagen alpha-1 | 195 | 60 | 40.81 | 49.3 | −0.778 | 180,196.21 | A0A6J2VX00 |
Hemoglobin | 14 | 7 | 25.69 | 90.07 | −0.044 | 15,644.13 | A0A6J2WNB3 |
Myoglobin | 15 | 17 | 10.36 | 102.31 | 0.095 | 15,667.24 | B9A9V0 |
Tropomyosin | 79 | 4 | 45.54 | 81.9 | −1.032 | 32,984.17 | A0A6J2VHL7 |
Troponin T | 76 | 65 | 85.2 | 58.93 | −1.525 | 33,986.17 | A0A6J2VB81 |
Parvalbumin | 20 | 13 | 27.35 | 79.91 | −0.043 | 11,613.04 | A0A6J2UQU6 |
Calponin | 36 | 34 | 41.9 | 61.77 | −0.728 | 34,072.12 | A0A6J2WNF1 |
Actin | 50 | 37 | 34.36 | 82.81 | −0.221 | 41,974.92 | A0A6J2VUG0 |
Enzyme | ∑AE | |||||
---|---|---|---|---|---|---|
Antioxidative | ACE Inhibitor | DPPIV Inhibitor | Anti-Amnesia | Renin Inhibitor | Antithrombotic | |
Papain | 0.0343 | 0.5563 | 0.667 | 0.0237 | 0.0211 | 0.0231 |
Bromelain | 0.033 | 0.5585 | 0.5983 | 0.0484 | 0.0377 | 0.0484 |
Ficin | 0.0694 | 2.2332 | 3.2131 | 0.0371 | 0.0644 | 0.0365 |
No. | Peptide | ACE-Inhibitory Score | Antihypertensive Score | Antidiabetic Score | DPPIV-Inhibitory Score |
---|---|---|---|---|---|
1 | PMNPPK | 0.977 | − | − | − |
2 | VNPYKWL | 0.663 | − | − | − |
3 | AAPNF | 0.51 | − | − | − |
4 | PPPPV | 0.582 | − | − | − |
5 | PMIPG | − | 0.818 | − | − |
6 | YPPPT | − | 0.837 | − | − |
7 | AMYF | 0.528 | 0.903 | − | − |
8 | PPPS | 0.591 | 0.957 | − | − |
9 | MVWH | 0.612 | 0.936 | − | − |
10 | AAWMIY | − | 0.778 | 0.574 | − |
11 | AWMIYT | − | 0.517 | 0.519 | − |
12 | MQML | − | − | 0.813 | 0.594 |
No | Peptide | HADDOCK Score | Cluster | RMSD (Å) | Z-Score |
---|---|---|---|---|---|
1 | MQML | −52.7 +/− 1.7 | 2 | 0.7 +/− 0.1 | −1.4 |
2 | AAPNF | −53.5 +/− 10.4 | 7 | 1.0 +/− 0.1 | −1.8 |
3 | PPPPV | −62.2 +/− 4.8 | 7 | 0.5 +/− 0.1 | −2.4 |
4 | YPPPT | −65.5 +/− 1.9 | 4 | 0.9 +/− 0.1 | −1.8 |
5 | PMNPPK | −66.0 +/− 2.2 | 4 | 0.2 +/− 0.1 | −2.2 |
6 | PPPS | −67.6 +/− 1.9 | 2 | 0.3 +/− 0.2 | −1.9 |
7 | PMIPG | −72.8 +/− 0.5 | 2 | 0.3 +/− 0.2 | −1.9 |
8 | AWMIYT | −82.2 +/− 2.6 | 1 | 0.6 +/− 0.1 | −1 |
9 | AAWMIY | −89.4 +/− 1.9 | 1 | 0.5 +/− 0.2 | −1.6 |
10 | VNPYKWL | −90.4 +/− 4.6 | 1 | 0.2 +/− 0.1 | −2.5 |
11 | AMYF | −92.9 +/− 2.0 | 4 | 0.7 +/− 0.0 | −1.7 |
12 | MVWH | −97.0 +/− 1.2 | 13 | 0.1 +/− 0.1 | −2 |
Peptides | Activity | Binding Affinity ΔG (kcal mol−1) | Kd (M) at 25 °C |
---|---|---|---|
VNPYKWL | ACE-I | −9.6 | 8.80 × 10−8 |
PMNPPK | ACE-I | −9.9 | 5.60 × 10−8 |
PPPPV | ACE-I | −12.3 | 9.30 × 10−10 |
PMIPG | ACE-I | −10.6 | 1.60 × 10−8 |
YPPPT | ACE-I | −10.4 | 2.20 × 10−8 |
AAPNF | ACE-I | −8.5 | 5.60 × 10−7 |
AMYF | ACE-I | −10.9 | 1.00 × 10−8 |
MVWH | ACE-I | −11 | 8.00 × 10−9 |
PPPS | ACE-I | −8.8 | 3.60 × 10−7 |
AWMIYT | DPPIV-I | −9.7 | 7.60 × 10−8 |
AAWMIY | DPPIV-I | −9.1 | 2.20 × 10−7 |
MQML | DPPIV-I | −8.6 | 4.80 × 10−7 |
ACE-Inhibitory Peptide | Interacting Residue and Position | Active Site Pocket | Interaction Type |
---|---|---|---|
VNPYKWL | Glu 162 | S1′ | HA, SB |
Glu 376 | HA, SB | ||
Asp 377 | SB | ||
Thr 372 | HA | ||
Cys 370 | HA | ||
Asn 285 | HA | ||
YPPPT | Lys 511 | S2 | HD |
Thr 166 | HD | ||
Asn 374 | HA, HD | ||
PPPPV | His 353 | S2 | HA |
Glu 162 | S1′ | HA, SB | |
Asn 285 | HD | ||
Thr 302 | HD | ||
PMIPG | Glu 376 | SB | |
Asn 285 | HA | ||
Ser 284 | HA | ||
Lys 449 | HD | ||
AAPNF | Glu 376 | HA | |
Asn 374 | HD | ||
Ala 354 | S1 | HD | |
Glu 384 | S1 | SB | |
Tyr 523 | S1 | HA | |
PMNPPK | Lys 449 | HD | |
Glu 376 | HD, SB | ||
Asp 453 | HA, SB | ||
Thr 282 | HA | ||
Ser 284 | HA | ||
MVWH | Gln 281 | S2 | HD |
Asp 377 | HA, HA, SB | ||
Lys 511 | S2 | HD | |
His 383 | Tetra-coordinated Zn | Pi | |
Glu 384 | S1 | HA | |
His 353 | S2 | Pi | |
AMYF | Asp 453 | HA | |
His 353 | S2 | HD | |
PPPS | Glu 384 | S1 | HA, SB |
Glu 411 | Tetra-coordinated Zn | SB | |
Tyr 523 | S1 | HA | |
Ala 354 | S1 | HD |
DPPIV-Inhibitory Peptide | Interacting Residue | Active Site Pocket | Interaction Type |
---|---|---|---|
AAWMIY | Glu 206 | S2 | HA |
Glu 205 | S2 | HA | |
Ser 209 | S3 | HA | |
Arg 125 | S2 | HD, Pi-c | |
Trp 629 | Pi | ||
Tyr 752 | HA | ||
AWMIYT | Arg 125 | S2 | Pi-c, Pi-c |
Glu 206 | S2 | HA | |
Ser 209 | S3 | HA | |
Tyr 585 | HD, Pi | ||
Arg 356 | HD | ||
Phe 357 | HD, Pi | ||
Arg 358 | S3 | HA | |
MQML | His 126 | HD | |
Arg 125 | S2 | HD | |
Ser 209 | S3 | HD | |
Arg 358 | S3 | HD |
Peptide | Absorption | Distribution | Toxicity | |||
---|---|---|---|---|---|---|
a MDCK | b HIA | c VD (L/Kg) | d PPB (%) | e HHT | f Ames | |
VNPYKWL | 3.5 × 10−5 | Low | 0.426 | 31.35 | Yes | No |
PMNPPK | 4.9 × 10−6 | Low | 0.617 | 19 | Yes | No |
PPPPV | 3.4 × 10−6 | Low | 0.425 | 21.67 | Yes | No |
AAPNF | 6.4 × 10−4 | Low | 0.283 | 8.31 | No | No |
YPPPT | 1.5 × 10−4 | Low | 0.369 | 33.84 | Yes | No |
PMIPG | 1.7 × 10−6 | Low | 0.418 | 12.11 | Yes | No |
AMYF | 4.4 × 10−6 | Low | 0.262 | 36 | Yes | No |
PPPS | 6.2 × 10−5 | Low | 0.422 | 14.85 | Yes | No |
MVWH | 1.7 × 10−6 | High | 0.318 | 19.86 | No | No |
AAWMIY | 2 × 10−6 | High | 0.331 | 65.25 | Yes | No |
AWMIYT | 2.2 × 10−6 | High | 0.366 | 62.72 | Yes | No |
MQML | 7.1 × 10−6 | High | 0.465 | 12.86 | No | No |
Peptide | a MW (<500 Da) | b HBAs (≤10) | c HBDs (≤5) | d logP (≤5) | e TPSA (≤140) | f RO5 Violation |
---|---|---|---|---|---|---|
VNPYKWL | 918.5 | 20 | 14 | 0.417 | 334.26 | 4 |
PMNPPK | 682.35 | 16 | 9 | −3.067 | 246.36 | 4 |
PPPPV | 505.29 | 11 | 3 | −2.066 | 139.36 | 2 |
AAPNF | 518.25 | 13 | 8 | −2.042 | 214.02 | 3 |
YPPPT | 573.28 | 13 | 6 | −1.391 | 193.81 | 3 |
PMIPG | 513.26 | 11 | 5 | −1.02 | 156.94 | 3 |
AMYF | 530.22 | 10 | 7 | 0.568 | 170.85 | 3 |
PPPS | 396.2 | 10 | 4 | −3.053 | 139.28 | 0 |
MVWH | 571.26 | 12 | 8 | 0.342 | 195.09 | 3 |
AAWMIY | 753.35 | 15 | 10 | 0.944 | 244.84 | 3 |
AWMIYT | 783.36 | 16 | 11 | 0.592 | 265.07 | 4 |
MQML | 521.23 | 11 | 8 | −0.222 | 193.71 | 3 |
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Nugraha, R.; Kurniawan, F.; Abdullah, A.; Lopata, A.L.; Ruethers, T. Antihypertensive and Antidiabetic Drug Candidates from Milkfish (Chanos chanos)—Identification and Characterization through an Integrated Bioinformatic Approach. Foods 2024, 13, 2594. https://doi.org/10.3390/foods13162594
Nugraha R, Kurniawan F, Abdullah A, Lopata AL, Ruethers T. Antihypertensive and Antidiabetic Drug Candidates from Milkfish (Chanos chanos)—Identification and Characterization through an Integrated Bioinformatic Approach. Foods. 2024; 13(16):2594. https://doi.org/10.3390/foods13162594
Chicago/Turabian StyleNugraha, Roni, Fahmi Kurniawan, Asadatun Abdullah, Andreas L. Lopata, and Thimo Ruethers. 2024. "Antihypertensive and Antidiabetic Drug Candidates from Milkfish (Chanos chanos)—Identification and Characterization through an Integrated Bioinformatic Approach" Foods 13, no. 16: 2594. https://doi.org/10.3390/foods13162594