Next Article in Journal
Alpha Lipoic Acid: A Therapeutic Strategy that Tend to Limit the Action of Free Radicals in Transplantation
Previous Article in Journal
Allyl Isothiocyanate Exhibits No Anticancer Activity in MDA-MB-231 Breast Cancer Cells
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(1), 141; doi:10.3390/ijms19010141

Computational Investigation of the Missense Mutations in DHCR7 Gene Associated with Smith-Lemli-Opitz Syndrome

1,†
,
2,†
,
3,†
and
1,*
1
Department of Physics and Astronomy, Clemson University, Clemson, SC 29630, USA
2
Department of Healthcare Genetics, Clemson University, Clemson, SC 29630, USA
3
Department of Chemistry, Clemson University, Clemson, SC 29630, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 16 November 2017 / Revised: 29 December 2017 / Accepted: 30 December 2017 / Published: 4 January 2018
View Full-Text   |   Download PDF [3190 KB, uploaded 4 January 2018]   |  

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol synthesis disorder characterized by physical, mental, and behavioral symptoms. It is caused by mutations in 7-dehydroxycholesterolreductase gene (DHCR7) encoding DHCR7 protein, which is the rate-limiting enzyme in the cholesterol synthesis pathway. Here we demonstrate that pathogenic mutations in DHCR7 protein are located either within the transmembrane region or are near the ligand-binding site, and are highly conserved among species. In contrast, non-pathogenic mutations observed in the general population are located outside the transmembrane region and have different effects on the conformational dynamics of DHCR7. All together, these observations suggest that the non-classified mutation R228Q is pathogenic. Our analyses indicate that pathogenic effects may affect protein stability and dynamics and alter the binding affinity and flexibility of the binding site. View Full-Text
Keywords: Smith-Lemli-Opitz syndrome; missense mutations; DHCR7; binding free energy; folding free energy; KNN classification; molecular dynamics simulation; MM/PBSA Smith-Lemli-Opitz syndrome; missense mutations; DHCR7; binding free energy; folding free energy; KNN classification; molecular dynamics simulation; MM/PBSA
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Peng, Y.; Myers, R.; Zhang, W.; Alexov, E. Computational Investigation of the Missense Mutations in DHCR7 Gene Associated with Smith-Lemli-Opitz Syndrome. Int. J. Mol. Sci. 2018, 19, 141.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top