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ECEL1 novel mutation in Arthrogryposis Type 5D: A Molecular Dynamic Simulation Study
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  • Najmeh Ahangari,
  • Nazanin Gholampour-Faroji,
  • Mohammad Doosti,
  • Majid Ghayour Mobarhan,
  • sima Shahrokhzadeh,
  • Ehsan Ghayoor Karimiani,
  • Bahareh Hasani sabzevar,
  • Paria Najarzadeh Torbati,
  • Aliakbar Haddad-Mashadrizeh
Najmeh Ahangari
Department of Medical Genetic & Molecular Medicine, Faculty of Medicine, Mashhad University of medical sciences, Iran
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Nazanin Gholampour-Faroji
Biotechnology Department, Iranian Research Organization for Science and Technology (IROST)
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Mohammad Doosti
Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.
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Majid Ghayour Mobarhan
Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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sima Shahrokhzadeh
Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran.
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Ehsan Ghayoor Karimiani
Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad
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Bahareh Hasani sabzevar
Advanced computational center, Khayyam Innovation Ecosystem, Mashhad, Iran
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Paria Najarzadeh Torbati
Next Generation Genetic Polyclinic, Mashad, Iran
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Aliakbar Haddad-Mashadrizeh
Industrial Biotechnology Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
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Abstract

Background: ECEL1 has been represented as a causal gene of an autosomal recessive form distal arthrogryposis (DA) which affects the distal joints. The present study focused on bioinformatic analysis of a novel mutation in ECEL1, c.535A>G (p. Lys179Glu), which reported in a family with 2 affected boy and fetus through prenatal diagnosis. Material and Methods: Whole exome sequencing data analyzed followed by Molecular Dynamics (MD) simulation of native ECEL1 protein and mutant structures using GROMACS software. Results: One variant c.535A>G, p. Lys179Glu (Homozygous) on gene ECEL1 has been detected in proband which was segregated in all family members. we demonstrated remarkable constructional differences by MD simulation between wild type and novel mutant of ECEL1 gene.the reason of the lack of the Zn ion binding in mutation in the ECEL1 protein have been identified by average atomic distance and SMD analysis among the wild type and mutant Conclusion: Overall, our findings in this study we present aknowledge of the effect of the mutation on the ECEL1 protein leading towards the fatal neurodegenerative disorder in humans. This work may hopefully be supplementary to classical molecular dynamics to dissolve the mutational effects of cofactor dependent protein, since the second one is time consuming and laborious.