[Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin].
OBJECTIVE
To investigate the mechanism of binding of human serum albumin (HSA) with potential sensitinogen, including chlorogenic acid and two isochlorogenic acids (3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid).


METHODS
By using the docking algorithm of computer-aided molecular design and the Molegro Virtual Docker, the crystal structures of HSA with warfarin and diazepam (Protein Data Bank ID: 2BXD and 2BXF) were selected as molecular docking receptors of HSA sites I and II. According to docking scores, key residues and H-bond, the molecular docking mode was selected and confirmed. The molecular docking of chlorogenic acid and two isochlorogenic acids on sites I and II was compared based on the above design.


RESULTS
The results from molecular docking indicated that chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid could bind to HSA site I by high affinity scores of -112.3, -155.3 and -153.1, respectively. They could bind to site II on HSA by high affinity scores of -101.7, -138.5 and -133.4, respectively. In site I, two isochlorogenic acids interacted with the key apolar side-chains of Leu238 and Ala291 by higher affinity scores than chlorogenic acid. Furthermore, the H-bonds of isochlorogenic acids with polar residues inside the pocket and at the entrance of the pocket were different from chlorogenic acid. Moreover, the second coffee acyl of isochlorogenic acid occupied the right-hand apolar compartment in the pocket of HSA site I. In site I, the second coffee acyl of isochlorogenic acid formed the H-bonds with polar side-chains, which contributed isochlorogenic acid to binding with site II of HSA.


CONCLUSIONS
The isochlorogenic acids with two coffee acyls have higher binding abilities with HSA than chlorogenic acid with one coffee acyl, suggesting that isochlorogenic acids binding with HSA may be sensitinogen.
Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, College of Pharmacy, Nanjing University of Chinese Medicine, China.
Jing
J
Zhou
Hong-yue
HY
Ma
Xin-sheng
XS
Fan
Wei
W
Xiao
Tuan-jie
TJ
Wang
D001665:Binding Sites; D002726:Chlorogenic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D017076:Computer-Aided Design; D015195:Drug Design; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry*
C500585:3,5-di-O-(E)-caffeoylquinic acid; D004365:Drugs, Chinese Herbal; D009005:Monosaccharides; D012709:Serum Albumin; D011801:Quinic Acid; D002726:Chlorogenic Acid; C478100:3,4-di-O-caffeoylquinic acid