PMID- 30463177
OWN - NLM
STAT- MEDLINE
DCOM- 20190723
LR  - 20190723
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 23
IP  - 11
DP  - 2018 Nov 19
TI  - Prediction of GluN2B-CT(1290-1310)/DAPK1 Interaction by Protein(-)Peptide Docking 
      and Molecular Dynamics Simulation.
LID - 10.3390/molecules23113018 [doi]
LID - 3018
AB  - The interaction of death-associated protein kinase 1 (DAPK1) with the 2B subunit 
      (GluN2B) C-terminus of N-methyl-D-aspartate receptor (NMDAR) plays a critical 
      role in the pathophysiology of depression and is considered a potential target 
      for the structure-based discovery of new antidepressants. However, the 3D 
      structures of C-terminus residues 1290(-)1310 of GluN2B (GluN2B-CT(1290-1310)) 
      remain elusive and the interaction between GluN2B-CT(1290-1310) and DAPK1 is 
      unknown. In this study, the mechanism of interaction between DAPK1 and 
      GluN2B-CT(1290-1310) was predicted by computational simulation methods including 
      protein(-)peptide docking and molecular dynamics (MD) simulation. Based on the 
      equilibrated MD trajectory, the total binding free energy between 
      GluN2B-CT(1290-1310) and DAPK1 was computed by the mechanics generalized born 
      surface area (MM/GBSA) approach. The simulation results showed that hydrophobic, 
      van der Waals, and electrostatic interactions are responsible for the binding of 
      GluN2B-CT(1290(-)1310)/DAPK1. Moreover, through per-residue free energy 
      decomposition and in silico alanine scanning analysis, hotspot residues between 
      GluN2B-CT(1290-1310) and DAPK1 interface were identified. In conclusion, this 
      work predicted the binding mode and quantitatively characterized the 
      protein(-)peptide interface, which will aid in the discovery of novel drugs 
      targeting the GluN2B-CT(1290-1310) and DAPK1 interface.
FAU - Tu, Gao
AU  - Tu G
AD  - Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical 
      Sciences and Collaborative Innovation Center for Brain Science, Chongqing 
      University, Chongqing 401331, China. tugao@cqu.edu.cn.
AD  - Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical 
      Sciences, Zhejiang University, Hangzhou 310058, China. tugao@cqu.edu.cn.
FAU - Fu, Tingting
AU  - Fu T
AD  - Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical 
      Sciences and Collaborative Innovation Center for Brain Science, Chongqing 
      University, Chongqing 401331, China. 20162902031@cqu.edu.cn.
AD  - Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical 
      Sciences, Zhejiang University, Hangzhou 310058, China. 20162902031@cqu.edu.cn.
FAU - Yang, Fengyuan
AU  - Yang F
AD  - Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical 
      Sciences and Collaborative Innovation Center for Brain Science, Chongqing 
      University, Chongqing 401331, China. kristen@cqu.edu.cn.
AD  - Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical 
      Sciences, Zhejiang University, Hangzhou 310058, China. kristen@cqu.edu.cn.
FAU - Yao, Lixia
AU  - Yao L
AD  - Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA. 
      ballad2006@163.com.
FAU - Xue, Weiwei
AU  - Xue W
AUID- ORCID: 0000-0002-3285-0574
AD  - Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical 
      Sciences and Collaborative Innovation Center for Brain Science, Chongqing 
      University, Chongqing 401331, China. xueww@cqu.edu.cn.
FAU - Zhu, Feng
AU  - Zhu F
AUID- ORCID: 0000-0001-8069-0053
AD  - Innovative Drug Research and Bioinformatics Group, School of Pharmaceutical 
      Sciences and Collaborative Innovation Center for Brain Science, Chongqing 
      University, Chongqing 401331, China. zhufeng@cqu.edu.cn.
AD  - Innovative Drug Research and Bioinformatics Group, College of Pharmaceutical 
      Sciences, Zhejiang University, Hangzhou 310058, China. zhufeng@cqu.edu.cn.
LA  - eng
GR  - 81872798, 21505009/National Natural Science Foundation of China/
GR  - cstc2015zdcy-ztzx120003/Innovation Project on Industrial Generic Key Technologies 
      of Chongqing/
GR  - 10611CDJXZ238826, 2018CDQYSG0007/Fundamental Research Funds for Central 
      Universities/
PT  - Journal Article
DEP - 20181119
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
MH  - *Death-Associated Protein Kinases
MH  - Humans
MH  - Hydrogen Bonding
MH  - Hydrophobic and Hydrophilic Interactions
MH  - *Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Protein Binding
MH  - *Receptors, N-Methyl-D-Aspartate
MH  - Thermodynamics
PMC - PMC6278559
OTO - NOTNLM
OT  - DAPK1-GluN2B peptide
OT  - MD simulation
OT  - binding free energy
OT  - hotspot
OT  - protein-peptide docking
COIS- The authors declare that they have no conflicts of interest to disclose.
EDAT- 2018/11/23 06:00
MHDA- 2019/07/25 06:00
PMCR- 2018/11/19
CRDT- 2018/11/23 06:00
PHST- 2018/08/20 00:00 [received]
PHST- 2018/11/04 00:00 [revised]
PHST- 2018/11/06 00:00 [accepted]
PHST- 2018/11/23 06:00 [entrez]
PHST- 2018/11/23 06:00 [pubmed]
PHST- 2019/07/25 06:00 [medline]
PHST- 2018/11/19 00:00 [pmc-release]
AID - molecules23113018 [pii]
AID - molecules-23-03018 [pii]
AID - 10.3390/molecules23113018 [doi]
PST - epublish
SO  - Molecules. 2018 Nov 19;23(11):3018. doi: 10.3390/molecules23113018.