The Quantitative Structure Activity Relationships Of Angiotensin Converting Enzyme Inhibitor Peptide From Egg White

In order to understand the Quantitative Structure Activity Relationships (QSAR)and inhibitor mechanism of Angiotensin converting enzyme inhibitor peptide（ACEIP）。The whole research was divided into two parts.1) collecting the inhibitordata of ACEIP,2) studying the QSAR and inhibitor mechanism.In the first part, there methods were used for collecting the inhibitor data ofACEIP,.1) Identify novel peptide. ACEIPs were purified and identified from egg whiteprotein hydrolysate by size-exclusion chromatography and LC-MS/MS. Two novelACE-inhibitory peptides were identified as IRL and VKY. The values of IC50were117.34μM and4.56μM, respectively.(refer to Chapter2)2) Reform peptides. Twenty six novel ACEIPs were designed by replacing theamino acid residues of RVPSL by Ala. All the peptides were synthesized and purifiedto95%by HPLC. The IC50value of these peptides ranged from9.5μmol/L to640μmol/L. The result indicate that the IC50value may relate to hydrophilicity,molecular volume.(refer to Chapter3)3) Collecting data from former works. Collect the data from former work andselect some which could be employed for QSAR.(refer to Chapter4and Chapter5)In the second part, four methods are used for studying the QSAR and inhibitormechanism..1) Using amino acids descriptors. The3Z amino acids descriptors wereemployed to code the peptides. And three-layer back-propagation neural network model was used to predict the structure of angiotensin-converting enzyme inhibitorytripeptide. The model has a high predictive ability when the topology structure is9-3-1and the transfer function were tan-sigmoid＆liner transfer. The IC50of the threemost potent ACE inhibitory peptides (Thr-Lys-Tyr, Lys-Arg-Try, Arg-Gln-Tyr) of thismodel was1.1μm,18.3μM174.6μM, respectively.2) Using peptides descriptors. The peptides were coded by peptide descriptorswith the discovery studios. And the QSAR functions were build by combining GA andGenetic Algorithms (GA) and Multiple linear regression (MLR). The result showedthat the most important factor should be the polar surface area radio.3) Molecular docking. CDocker was employed to docking all the26peptides inchapter3, and260poses were obtained. The result show that the interaction betweenpeptides and Zn atom in ACE may the most important factor. And other factors haslittle effect.4）Molecular dynamics. Molecular dynamics was carried out by GROMACSprograme. According to the result, it can found that the peptides were all binding onone side of the zinc atom which might be formed by coordination. What’s morehydrogen bonds also act as an important role in keeping the stability of the complexstructure.