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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (10): 1149-1154.doi: 10.3736/jcim20121012

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Molecular docking of chlorogenic acid, 3,4-di-O-caffeoylquinic acid and 3,5-di-O-caffeoylquinic acid with human serum albumin

Jing Zhou1, Hong-yue Ma1, Xin-sheng Fan1(), Wei Xiao2,3(), Tuan-jie Wang2,3   

  1. 1. Jiangsu Key Laboratory for Traditional Chinese Medicine Formulae Research, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, Jiangsu Province, China
    2. Jiangsu Kanion Parmaceutical CO. LTD, Lianyungang 222001, Jiangsu Province, China
    3. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Lianyungang 222001, Jiangsu Province, China
  • Received:2012-04-13 Accepted:2012-05-18 Online:2012-10-20 Published:2018-10-15
  • Contact: Xin-sheng Fan, Wei Xiao;

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 Ⅱ, 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.

Conclusion: 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.

Key words: plant extracts, chlorogenic acid, isochlorogenic acid, human serum albumin, molecular docking, computer-aided design

Table 1

Docking method validation"

Ligand Protein (PDB ID) Site RMSD MD score Rerank score H bond score Key residues
Warfarin HSA (2BXD) Site Ⅰ 0.47 –108.5 –93.2 –7.7 Tyr150, Arg222, His242
Diazepam HSA (2BXF) Site Ⅱ 0.45 –107.9 –91.5 –1.9 Tyr411
Warfarin HSA (2BXF) Site Ⅱ –112.7 –88.9 –0.1
Diazepam HSA (2BXD) Site Ⅰ –80.7 –67.4 –2.1 Tyr150

Table 2

Docking scores and interaction residues of tested compounds binding to HSA (PDB ID: 2BXD) site Ⅰ"

Ligand MD score Rerank score H bond score Key residues (score)
Chlorogenic acid –112.3 –108.1 –12.8 Tyr150 (–16.4), Arg257 (–14.0), Ala291 (–11.7),Lys199 (–11.5), Gln196 (–9.3), Leu238 (–4.4)
3,4-di-O-Caffeoylquinic acid –155.3 –111.4 –12 Ala291 (–17.0), Arg257 (–16.8), Leu238 (–15.4), Tyr150 (–13.6), Lys199 (–11.5), His242 (–10.7), His288 (–10.1)
3,5-di-O-Caffeoylquinic acid –153.1 –128.4 –13.6 Tyr150 (–19.5), Ser192 (–16.0), Lys199 (–15.5), Lys 195 (–14.9), Leu238 (–13.6), Ala291 (–12.8), Arg257 (–10.0), His242 (–8.9); Arg222 (–5.8)

Figure 1

Molecular docking model (A1-C1) and interaction residues (A2-C2) of chlorogenic acid (A), 3,4-di-O-caffeoylquinic acid (B) and 3,5-di-O-caffeoylquinic acid (C) binding to HSA site Ⅰ Apolar chains were marked in blue; semipolar chains were marked in violet; polar chains were marked in red. The H-bonds were marked in green dash line. HSA: human serum albumin. "

Table 3

Docking scores and interaction residues of tested compounds binding to HSA (PDB ID: 2BXF) site Ⅱ"

Ligand MD score Rerank score H bond score Key residues (score)
Chlorogenic acid –101.7 –90.4 –9.5 Asn391 (–21.6), Leu387 (–14.9), Ile388 (–14.8), Val433 (–13.7), Leu453 (–9.5), Leu430 (–9.1), Arg485 (–7.1), Tyr411 (–6.8), Ser489 (–6.5)
4-di-O-Caffeoylquinic acid –138.5 –101.7 –5.8 Tyr411 (–20.1), Leu387 (–18.1), Asn391 (–17.4), Arg485 (–13.5), Ile388 (–11.7), Val433 (–10.6), Leu453 (–10.2), Ser489 (–9.2), Pro384 (–7.6), Leu430(–7.0)
3,5-di-O-Caffeoylquinic acid –133.4 –91.7 –13.2 Asn391 (–29.3), Leu387 (–15.8), Ile388 (–14.8), Val433 (–14.4), Tyr411 (–11.4), Gln390 (–10.8), Ser489 (–10.7), Arg410 (–10.3), Leu453 (–10.1), Leu430 (–8.8)

Figure 2

Molecular docking model (A1-C1) and interaction residues (A2-C2) of chlorogenic acid (A), 3,4-di-O-caffeoylquinic acid (B) and 3,5-di-O-caffeoylquinic acid (C) binding to HSA site ⅡApolar chains were marked in blue; semipolar chains were marked in violet; polar chains were marked in red. The H-bonds were marked in green dash line. HSA: human serum albumin."

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