PMID- 38095566
OWN - NLM
STAT- Publisher
LR  - 20231214
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
DP  - 2023 Dec 14
TI  - Queuine as a potential multi-target drug for alzheimer's disease: insights from 
      protein dynamics.
PG  - 1-22
LID - 10.1080/07391102.2023.2293262 [doi]
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with a complex 
      pathogenesis. One promising approach to treating AD is simultaneously targeting 
      multiple aspects of the disease using a multi-target drug (MTD). In this study, 
      multi-target drug (MTD) potential of the nutraceutical molecule Queuine was 
      explored using molecular docking and molecular dynamics (MD) simulations with 
      five different protein targets engaged in AD: AChE, beta-site amyloid precursor 
      protein cleaving enzyme-1 (BACE-1), N-methyl-D-aspartate receptor (NMDAR), 
      monoamine oxidase A (MAO-A), and Synapsin III. Queuine revealed significant 
      binding affinities, the docking scores being -10.1, -5.97, -5.63, -8.40, and 
      -10.56 kcal/mol for AChE, BACE-1, NMDAR, MAO-A, and Synapsin III, respectively. 
      MD simulations showed that Queuine formed stable complexes and preserved its 
      stability throughout the simulation, the backbone fluctuations remaining within 
      2.5 A specifically in the case of the BACE-1. Elastic network model simulations 
      and principal component analysis were carried out to illustrate the dynamics of 
      the protein systems. Significant hinge-bending and twisting-type motions that may 
      be relevant to function were observed around the dimerization interfaces or 
      binding sites. Structural clustering based on PCA analysis and cross-correlation 
      maps demonstrated that Queuine binding altered the protein dynamics more 
      drastically in the case of highly mobile proteins NMDAR and MAO-A. We propose 
      that the neuroprotective effect of Queuine may stem from its prominent inhibitory 
      action on enzymes BACE-1 and AChE. Our results suggest that Queuine may serve as 
      a promising MTD candidate for the treatment of AD.Communicated by Ramaswamy H. 
      Sarma.
FAU - Girgin, Munteha
AU  - Girgin M
AD  - Department of Chemical Engineering, Uskudar University, Istanbul, Turkey.
FAU - Kantarci-Carsibasi, Nigar
AU  - Kantarci-Carsibasi N
AUID- ORCID: 0000-0003-1013-6668
AD  - Department of Chemical Engineering, Uskudar University, Istanbul, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20231214
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
SB  - IM
OTO - NOTNLM
OT  - Acetylcholinesterase
OT  - N-methyl-D-aspartate receptor
OT  - beta-site amyloid precursor protein cleaving enzyme-1
OT  - monoamine oxidase A
OT  - multi-target drug
OT  - synapsin III
EDAT- 2023/12/14 12:42
MHDA- 2023/12/14 12:42
CRDT- 2023/12/14 10:03
PHST- 2023/12/14 12:42 [medline]
PHST- 2023/12/14 12:42 [pubmed]
PHST- 2023/12/14 10:03 [entrez]
AID - 10.1080/07391102.2023.2293262 [doi]
PST - aheadofprint
SO  - J Biomol Struct Dyn. 2023 Dec 14:1-22. doi: 10.1080/07391102.2023.2293262.