Quantitative Structure-Activity Relationship Modeling Coupled with Molecular Docking Analysis in Screening of
Kai Lin1, Lanwei Zhang1,2,3, Xue Han1
1School of Chemistry and Chemical Engineering , Harbin Institute of Technology , Harbin 150000 , China.
Abstract:
In this study, Qula casein derived from yak milk casein was hydrolyzed using a two-enzyme combination approach, and high angiotensin I-converting enzyme (ACE) inhibitory activity peptides were screened by quantitative structure-activity relationship (QSAR) modeling integrated with molecular docking analysis. Hydrolysates (<3 kDa) derived from combinations of thermolysin + alcalase and thermolysin + proteinase K demonstrated high ACE inhibitory activities. Peptide sequences in hydrolysates derived from these two combinations were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). On the basis of the QSAR modeling prediction, a total of 16 peptides were selected for molecular docking analysis. The docking study revealed that four of the peptides (KFPQY, MPFPKYP, MFPPQ, and QWQVL) bound the active site of ACE. These four novel peptides were chemically synthesized, and their IC50 was determined. Among these peptides, KFPQY showed the highest ACE inhibitory activity (IC50 = 12.37 ± 0.43 μM). Our study indicated that Qula casein presents an excellent source to produce ACE inhibitory peptides.
Related Concept Videos
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Enzymes
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzymes and Activation Energy
Enzyme Kinetics
Scientists typically study enzyme kinetics with a fixed amount of enzyme in the controlled environment of a test tube. When more reactant, or substrate, is...
Enzyme-linked Receptors
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...


