TY - JOUR
T1 - Predictive modelling of angiotensin converting enzyme inhibitory dipeptides
AU - Norris, Roseanne
AU - Casey, Fergal
AU - FitzGerald, Richard J.
AU - Shields, Denis
AU - Mooney, Catherine
PY - 2012/8/15
Y1 - 2012/8/15
N2 - The ability of docking to predict angiotensin converting enzyme (ACE) inhibitory dipeptide sequences was assessed using AutoDock Vina. All potential dipeptides and phospho-dipeptides were docked and scored. Peptide intestinal stability was assessed using a prediction amino acid clustering model. Selected dipeptides, having AutoDock Vina scores ≤ -8.1 and predicted to be 'stable' intestinally, were characterised, using LIGPLOT and for ACE-inhibitory potency. Two newly identified ACE-inhibitory dipeptides, Asp-Trp and Trp-Pro, having Vina scores of -8.3 and -8.6 gave IC 50 values of 258 ± 4.23 and 217 ± 15.7 μM, respectively. LIGPLOT analysis indicated no zinc interaction for these dipeptides. Phospho-dipeptides were predicted to have a good affinity for ACE. However, the experimentally determined IC 50 results did not correlate since, for example, Trp-pThr and Pro-pTyr, having Vina scores of -8.5 and -8.1, respectively, displayed IC 50 values of >500 μM. While docking allowed identification of new ACE inhibitory dipeptides, it may not be a fully reliable predictive tool in all cases.
AB - The ability of docking to predict angiotensin converting enzyme (ACE) inhibitory dipeptide sequences was assessed using AutoDock Vina. All potential dipeptides and phospho-dipeptides were docked and scored. Peptide intestinal stability was assessed using a prediction amino acid clustering model. Selected dipeptides, having AutoDock Vina scores ≤ -8.1 and predicted to be 'stable' intestinally, were characterised, using LIGPLOT and for ACE-inhibitory potency. Two newly identified ACE-inhibitory dipeptides, Asp-Trp and Trp-Pro, having Vina scores of -8.3 and -8.6 gave IC 50 values of 258 ± 4.23 and 217 ± 15.7 μM, respectively. LIGPLOT analysis indicated no zinc interaction for these dipeptides. Phospho-dipeptides were predicted to have a good affinity for ACE. However, the experimentally determined IC 50 results did not correlate since, for example, Trp-pThr and Pro-pTyr, having Vina scores of -8.5 and -8.1, respectively, displayed IC 50 values of >500 μM. While docking allowed identification of new ACE inhibitory dipeptides, it may not be a fully reliable predictive tool in all cases.
KW - ACE inhibition
KW - AutoDock Vina
KW - Dipeptides
KW - Intestinal stability
KW - Predictive modelling
UR - http://www.scopus.com/inward/record.url?scp=84859791745&partnerID=8YFLogxK
U2 - 10.1016/j.foodchem.2012.02.023
DO - 10.1016/j.foodchem.2012.02.023
M3 - Article
AN - SCOPUS:84859791745
SN - 0308-8146
VL - 133
SP - 1349
EP - 1354
JO - Food Chemistry
JF - Food Chemistry
IS - 4
ER -