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In silico discrimination of nsSNPs in hTERT gene by means of local DNA sequence context and regularity

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Abstract

Understanding and predicting the significance of novel genetic variants revealed by DNA sequencing is a major challenge to integrate and interpret in medical genetics with medical practice. Recent studies have afforded significant advances in characterization and predicting the association of single nucleotide polymorphisms in human TERT with various disorders, but the results remain inconclusive. In this context, a comparative study between disease causing and novel mutations in hTERT gene was performed computationally. Out of 59 missense mutations, five variants were predicted to be less stable with the most deleterious effect on hTERT gene by in silico tools, in which two mutations (L584W and M970T) were not previously reported to be involved in any of the human disorders. To get insight into the structural and functional impact due to the mutation, docking study and interaction analysis was performed followed by 6 ns molecular dynamics simulation. These results may provide new perspectives for the targeted drug discovery in the coming future.

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Acknowledgments

The authors take this opportunity to thank the management of Vellore Institute of Technology University for providing the facilities and encouragement to carry out this work.

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Authors and Affiliations

  1. Medical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India

    C. George Priya Doss, B. Rajith & N. Nagasundaram

  2. Department of Bio-informatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, India

    Chiranjib Chakraborty

Authors
  1. C. George Priya Doss
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  2. Chiranjib Chakraborty
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  3. B. Rajith
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  4. N. Nagasundaram
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Corresponding author

Correspondence to C. George Priya Doss.

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Supplementary Table 1

Summary of nsSNPs that were prioritized by in silico tools like SIFT, PolyPhen and I-Mutant 2.0. (DOC 88.0 kb)

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Doss, C.G.P., Chakraborty, C., Rajith, B. et al. In silico discrimination of nsSNPs in hTERT gene by means of local DNA sequence context and regularity. J Mol Model 19, 3517–3527 (2013). https://doi.org/10.1007/s00894-013-1888-7

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  • DOI: https://doi.org/10.1007/s00894-013-1888-7

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