In silico analysis predicting effects of deleterious SNPs of human RASSF5 gene on its structure and functions

Md Shahadat Hossain1, Arpita Singha Roy1, Md Sajedul Islam2

  • 1Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, Bangladesh.

Scientific Reports
|September 5, 2020
PubMed

Insights

Single nucleotide polymorphisms (SNPs) in Ras association domain-containing protein 5 (RASSF5) can disrupt its tumor suppressor function. This study identifies key RASSF5 SNPs impacting protein stability and interactions, offering potential diagnostic and therapeutic targets.

Area of Science:

  • Molecular Biology
  • Genetics
  • Bioinformatics

Background:

  • Ras association domain-containing protein 5 (RASSF5) is a vital tumor suppressor. Single nucleotide polymorphisms (SNPs) can alter protein function, potentially contributing to cancer development.
  • Understanding the impact of RASSF5 SNPs is crucial for identifying new biomarkers and therapeutic strategies in oncology.

Purpose of the Study:

  • To identify and analyze the most deleterious SNPs in RASSF5.
  • To predict structural changes caused by these SNPs and their effect on protein-protein interactions.
  • To investigate the potential of functional RASSF5 SNPs as targets for cancer diagnosis and therapy.

Main Methods:

  • Utilized sequence and structure-based bioinformatics approaches to analyze RASSF5 SNPs.
  • Employed six in silico SNP prediction tools to identify deleterious variants.
  • Performed stability analysis, energy minimization, docking analysis with H-Ras, and protein-protein interaction network analysis.

Main Results:

  • Identified 25 highly deleterious RASSF5 SNPs, with 17 found to decrease protein stability.
  • Observed significant energy deviations for P350R, F321L, and R277W mutations.
  • Docking analysis revealed that P350R, A319V, F321L, and R277W reduce binding affinity with H-Ras, with P350R showing the most significant impact. RASSF5 acts as a hub in protein interaction networks, and alterations can disrupt signaling cascades.

Conclusions:

  • Functional SNPs in RASSF5, particularly those affecting protein stability and H-Ras binding, are identified as potential targets for proteomic studies.
  • These findings support the exploration of RASSF5 SNPs for cancer diagnosis and therapeutic interventions.
  • The study highlights the importance of investigating genetic variations in tumor suppressor genes for understanding cancer mechanisms.

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