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Frontiers of Chemical Science and Engineering

ISSN 2095-0179

ISSN 2095-0187(Online)

CN 11-5981/TQ

Postal Subscription Code 80-969

2018 Impact Factor: 2.809

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Front. Chem. Sci. Eng.    2019, Vol. 13 Issue (1) : 133-139    https://doi.org/10.1007/s11705-018-1737-4
RESEARCH ARTICLE
Molecular simulation of the interaction mechanism between CodY protein and DNA in Lactococcus lactis
Linchen Yuan1,2, Hao Wu1,2, Yue Zhao1,2, Xiaoyu Qin1,2, Yanni Li1,2()
1. Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
2. Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, China
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Abstract

In Lactococcus lactis, the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.
Keywords CodY      DNA      molecular docking      molecular dynamics     
Corresponding Author(s): Yanni Li   
Just Accepted Date: 19 April 2018   Online First Date: 21 June 2018    Issue Date: 25 February 2019
 Cite this article:   
Linchen Yuan,Hao Wu,Yue Zhao, et al. Molecular simulation of the interaction mechanism between CodY protein and DNA in Lactococcus lactis[J]. Front. Chem. Sci. Eng., 2019, 13(1): 133-139.
 URL:  
https://academic.hep.com.cn/fcse/EN/10.1007/s11705-018-1737-4
https://academic.hep.com.cn/fcse/EN/Y2019/V13/I1/133
Fig.1  CodY dimer structure
Fig.2  The Z-score value of CodY
Parameter 1 2 3 4
Z-Score −1.3 −1.0 −0.9 −0.5
Haddock score −134.1±16.7 −126.4± 8.9 −123.2±11.0 −112.5±3.3
Cluster size 61 21 28 15
Van der Waals energy −74.5±11.4 −72.1±9.8 −71.9±2.2 −66.8±2.7
Electrostatic energy −513.9±44.7 −460.3±1.6 −432.0±48.3 −443.9±17.9
RMSD 6.9± 0.1 4.5±0.5 7.4±0.5 11.8±0.3
Buried surface area 1815.5 1845.6 1744.3 1796.7
Tab.1  Molecular Docking Results of HADDOCK
Fig.3  (a) The RMSD of CodY-DNA complexes; (b) the RMSF values of CodY-DNA (red) and CodY (blue)
Donor Acceptor Occupancy/%
SER219′-Side-OG DA16-Side-N3 99.75
ARG218′-Side-NH1 DT18-Side-OP1 99.53
GLY243-Main-N DC6-Side-OP1 99.00
ARG218-Side-NH2 DA5-Side-OP2 98.40
ARG218-Side-NE DA5-Side-OP2 95.85
SER186′-Main-N DC24-Side-OP1 94.51
LYS242-Side-NZ DA5-Side-OP1 91.52
SER184′-Side-OG DA24-Side-OP1 88.62
SER186′-Side-OG DC23-Side-O3′ 67.31
SER208-Side-OG DA5-Side-OP2 63.32
THR217′-Side-OG1 DT21-Side-O2 58.91
SER219-Side-OG DA7-Side-OP2 58.85
Tab.2  The hydrogen bonds between CodY and DNA
Fig.4  The hydrogen bonds between CodY and DNA. (a) SER208 and DA5, ARG218 and DA5; (b) SER219 and DA7; (c) LYS242 and DA5; (d) GLY243 and DC6; (e) SER184′ and DC24, SER186′ and DA23、DC24; (f) THR217′ and DT21; (g) ARG218′ and DT18; (h) SER219′ and DA16
DGVDW DGELE DGPB DGSA DGMM DGSOL DGTOT TDS DGbind
−96.15±1.93 −259.15±31.54 291.63±30.54 −19.78±0.13 −355.30±31.74 271.85±30.51 −83.45±2.33 −43.90±3.21 −39.55
Tab.3  Binding free energy of CodY-DNA complex/(kcal·mol−1)
Fig.5  Energetic contributions of key residues in CodY-DNA complex
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