Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese
Abstract
1. Introduction
2. Results and Discussion
2.1. Analysis of Physicochemical Properties of Peptides
2.2. Molecular Docking Analysis
2.3. Molecular Dynamics Analysis
2.3.1. GROMACS Analysis of the RMSD, RMSF, Hydrogen Bonds, SASA, and Gibbs Free Energy Stability Analysis
2.3.2. MM/GBSA Calculations and Analyses
The MM/GBSA Approach for Free Energy Estimation in Protein-Ligand Complexes
2.3.3. Dynamic Interaction Analysis from 0 to 100 ns via Molecular Simulations
2.4. Synthesis and Validation of PL Inhibitory Activity of Peptides RK7 and KQ7
2.4.1. In Vitro Validation of RK7 and KQ7’s Inhibitory Efficacy
2.4.2. Simulating the Effect of Gastrointestinal Digestion on PL Inhibition Activity
3. Materials and Methods
3.1. Materials and Reagents
3.2. Instruments and Equipment
3.3. Experimental Methods
3.3.1. Forecasting the Physicochemical Traits of Peptides RK7, KQ7, and TL9
3.3.2. Structure Adjustment and Optimization of RK7, KQ7, TL9 and PL
3.3.3. Molecular Docking
3.3.4. GROMACS Molecular Dynamics Simulation
3.3.5. PL Inhibition Experiments with Peptides RK7 and KQ7
3.3.6. Simulating the Impact of Gastrointestinal Digestion on PL Inhibitory Activity
3.3.7. Data Processing
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Peptide Sequence | Molecular Weight/(Da) | Isoelectric Point | Net Charge | Hydrophobic Amino Acids | Proportion of Hydrophobic Amino Acids |
---|---|---|---|---|---|
RK7 | 874.90 | 11.57 | 3 | P, I | 42.86% |
KQ7 | 779.50 | 9.84 | 1 | V, L, P | 71.42% |
TL9 | 968.19 | 3.32 | 0 | P, V, F, L | 88.91% |
RK7 | KQ7 | TL9 | Atorvastatin | |
---|---|---|---|---|
Hydrogen bonds | Val322, Asn320, Gln220, Glu188, Lys198, Gly321, His264 | Val325, Asp287, Glu188, Gln220, Ser323, Gly185 | Ser323, Gly223, Gln220, Gln22, Glu188, Val222, Pro194, Thr221 | Gln220, Glu188, Ser323, Pro194, Gly321, Pro194, Asp193, Val222, |
Hydrophobic interactions | Val325 | Val322, Phe228, Pro187 | Ile211, Ile210, Pro16, Val322, Pro194, Pro187, Leu189 | Val322, Arg164, Pro194 |
Van der Waals forces | Ala197, Gln324, Gly168, Asn167, Ser195, Arg164, Val222, Leu189, Gln220, Pro194, Gly223, Arg191, Asp193, Thr221, Ser323, Val322, Thr221, Tyr327, Lys318, Thr319 | Pro194, Asp193, Val222, Ser195, Gln324, Cys286, Tyr327, Asn167, Thr221, Ser219, Leu189, Pro16, Gly185, Thr186, Pro187, Thr186, Arg191, Gln22 | Pro209, Ala15, Arg191, Glu188, Asp193, Ser195, Ser219, Gly185, Thr186, Arg23, Gln184, Phe183, | Thr319, Ala197, Lys198, Gly168, Thr196, Asp196, Asn167, Ser195, Asp193, Thr221, Gly223, Glu188, A rg191, Val322, |
Electrostatic interactions | Glu188 | Glu188 | Arg191 | Arg191 |
(kcal/mol) | RK7 | KQ7 | TL9 |
---|---|---|---|
ΔVDWAALS | −71.11 ± 1.65 | −63.83 ± 2.46 | −49.54 ± 1.49 |
ΔEEL | −95.60 ± 1.35 | −19.66 ± 2.15 | −43.28 ± 3.35 |
ΔEGB | 65.11 ± 1.11 | 91.60 ± 3.06 | 70.12 ± 1.72 |
ΔEsurf | −10.12 ± 0.06 | −8.39 ± 0.07 | −6.88 ± 0.04 |
ΔGgas | −166.71 ± 2.13 | −83.49 ± 3.27 | −92.82 ± 3.67 |
ΔGsolv | 111.05 ± 0.52 | 47.95 ± 0.09 | 63.23 ± 1.72 |
ΔTotal | −55.66 ± 2.20 | −35.54 ± 3.27 | −29.59 ± 4.05 |
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Wang, P.; Song, X.; Liang, Q. Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese. Int. J. Mol. Sci. 2025, 26, 756. https://doi.org/10.3390/ijms26020756
Wang P, Song X, Liang Q. Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese. International Journal of Molecular Sciences. 2025; 26(2):756. https://doi.org/10.3390/ijms26020756
Chicago/Turabian StyleWang, Peng, Xuemei Song, and Qi Liang. 2025. "Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese" International Journal of Molecular Sciences 26, no. 2: 756. https://doi.org/10.3390/ijms26020756
APA StyleWang, P., Song, X., & Liang, Q. (2025). Molecular Docking Studies and In Vitro Activity of Pancreatic Lipase Inhibitors from Yak Milk Cheese. International Journal of Molecular Sciences, 26(2), 756. https://doi.org/10.3390/ijms26020756