PMID- 27762146
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20170316
IS  - 1029-046X (Electronic)
IS  - 1026-776X (Linking)
VI  - 27
IP  - 11
DP  - 2016 Nov
TI  - Combined QSAR-based virtual screening and fluorescence binding assay to identify 
      natural product mediators of Interferon Regulatory Factor 7 (IRF-7) in pulmonary 
      infection.
PG  - 967-976
AB  - Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and 
      pneumonia. Here, a synthetic strategy that combined quantitative 
      structure-activity relationship (QSAR)-based virtual screening and in vitro 
      binding assay was described to identify new and potent mediator ligands of IRF-7 
      from natural products. In the procedure, a QSAR scoring function was developed 
      and validated using Gaussian process (GP) regression and a structure-based set of 
      protein-ligand affinity data. By integrating hotspot pocket prediction, 
      pharmacokinetics profile analysis and molecular docking calculations, the scoring 
      function was successfully applied to virtual screening against a large library of 
      structurally diverse, drug-like natural products. With the method we were able to 
      identify a number of potential hits, from which several compounds were found to 
      have moderate or high affinity to IRF-7 using fluorescence binding assays, with 
      dissociation constants K(d) at micromolar level. We have also examined the 
      structural basis and noncovalent interactions of computationally modelled IRF-7 
      complex with its potent ligands. It is revealed that hydrophobic forces and van 
      der Waals contacts play a central role in stabilization of the complex 
      architecture, while few hydrogen bonds confer additional specificity for the 
      protein-ligand recognition.
FAU - Liu, Y
AU  - Liu Y
AD  - a Centre of Infectious Diseases , West China Hospital, Sichuan University , 
      Chengdu , China.
FAU - Huang, L
AU  - Huang L
AD  - a Centre of Infectious Diseases , West China Hospital, Sichuan University , 
      Chengdu , China.
FAU - Ye, H
AU  - Ye H
AD  - a Centre of Infectious Diseases , West China Hospital, Sichuan University , 
      Chengdu , China.
FAU - Lv, X
AU  - Lv X
AD  - a Centre of Infectious Diseases , West China Hospital, Sichuan University , 
      Chengdu , China.
LA  - eng
PT  - Journal Article
DEP - 20161020
PL  - England
TA  - SAR QSAR Environ Res
JT  - SAR and QSAR in environmental research
JID - 9440156
RN  - 0 (Biological Products)
RN  - 0 (Interferon Regulatory Factor-7)
RN  - 0 (Ligands)
SB  - IM
MH  - Biological Products/*chemistry/pharmacology
MH  - Fluorescence
MH  - Hydrogen Bonding
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Interferon Regulatory Factor-7/*metabolism
MH  - Ligands
MH  - Molecular Docking Simulation
MH  - Protein Binding
MH  - *Quantitative Structure-Activity Relationship
MH  - Respiratory Tract Infections/drug therapy/*metabolism
OTO - NOTNLM
OT  - Interferon regulatory factor-7
OT  - natural product
OT  - pneumonia
OT  - pulmonary infection
OT  - quantitative structure-activity relationship
EDAT- 2016/10/21 06:00
MHDA- 2017/03/17 06:00
CRDT- 2016/10/21 06:00
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
PHST- 2016/10/21 06:00 [entrez]
AID - 10.1080/1062936X.2016.1243576 [doi]
PST - ppublish
SO  - SAR QSAR Environ Res. 2016 Nov;27(11):967-976. doi: 
      10.1080/1062936X.2016.1243576. Epub 2016 Oct 20.