PMID- 33402819
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210111
IS  - 1177-9322 (Print)
IS  - 1177-9322 (Electronic)
IS  - 1177-9322 (Linking)
VI  - 14
DP  - 2020
TI  - Molecular Dynamics Simulation of T10609C and C10676G Mutations of Mitochondrial 
      ND4L Gene Associated With Proton Translocation in Type 2 Diabetes Mellitus and 
      Cataract Patients.
PG  - 1177932220978672
LID - 10.1177/1177932220978672 [doi]
LID - 1177932220978672
AB  - The mutation rate of mitochondrial DNA (mtDNA) is 17 times higher than nuclear 
      DNA, and these mutations can cause mitochondrial disease in 1 of 10.000 people. 
      The T10609C mutation was identified in type 2 diabetes mellitus (T2DM) patients 
      and the C10676G mutation in cataract patients, with both mutations occurring in 
      the ND4L gene of mtDNA that encodes ND4L protein. ND4L protein, a subunit of 
      complex I in the respiratory complex, has been shown to play a role in the proton 
      translocation process. The purpose of this study was to investigate the effect of 
      both mutations on the proton translocation mechanism. Mutation mapping showed 
      changes in amino acids M47T (T10609C) and C69W (C10676G). The 100 ns molecular 
      dynamics (MD) simulations performed on native and mutants of ND4L-ND6 subunits. 
      It is revealed that the native model had a similar proton translocation pathway 
      to that of complex I from other organisms. Interestingly, the mutant M47T and 
      C69W showed the interruption of the translocation pathway by a hydrogen bond 
      formation between Glu34 and Tyr157. It is observed that the mutations were 
      restricting the passage of water molecules through the transmembrane region. 
      These results could help to develop the computational assay for the validation of 
      a specific genetic biomarker for T2DM and cataracts.
CI  - (c) The Author(s) 2020.
FAU - Destiarani, Wanda
AU  - Destiarani W
AUID- ORCID: 0000-0003-1627-1553
AD  - Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas 
      Padjadjaran, Sumedang, Indonesia.
FAU - Mulyani, Rahmaniar
AU  - Mulyani R
AD  - Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas 
      Padjadjaran, Sumedang, Indonesia.
FAU - Yusuf, Muhammad
AU  - Yusuf M
AD  - Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas 
      Padjadjaran, Sumedang, Indonesia.
AD  - Research Center for Molecular Biotechnology and Bioinformatics, Universitas 
      Padjadjaran, Bandung, Indonesia.
FAU - Maksum, Iman Permana
AU  - Maksum IP
AUID- ORCID: 0000-0001-8166-8421
AD  - Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas 
      Padjadjaran, Sumedang, Indonesia.
LA  - eng
PT  - Journal Article
DEP - 20201216
PL  - United States
TA  - Bioinform Biol Insights
JT  - Bioinformatics and biology insights
JID - 101467187
PMC - PMC7747115
OTO - NOTNLM
OT  - C10676G
OT  - ND4L
OT  - T10609C
OT  - cataract
OT  - diabetes mellitus
OT  - proton translocation
COIS- Declaration of conflicting interests:The author(s) declared no potential con fl icts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2021/01/07 06:00
MHDA- 2021/01/07 06:01
PMCR- 2020/12/16
CRDT- 2021/01/06 05:52
PHST- 2020/08/15 00:00 [received]
PHST- 2020/11/14 00:00 [accepted]
PHST- 2021/01/06 05:52 [entrez]
PHST- 2021/01/07 06:00 [pubmed]
PHST- 2021/01/07 06:01 [medline]
PHST- 2020/12/16 00:00 [pmc-release]
AID - 10.1177_1177932220978672 [pii]
AID - 10.1177/1177932220978672 [doi]
PST - epublish
SO  - Bioinform Biol Insights. 2020 Dec 16;14:1177932220978672. doi: 
      10.1177/1177932220978672. eCollection 2020.