Molecular and Cellular Biochemistry

, Volume 409, Issue 1–2, pp 1–11 | Cite as

Computational investigation of molecular mechanism and neuropathological implications in Huntington disease

  • Chandrasekhar Gopalakrishnan
  • Namrata Kalsi
  • Shraddha Jethi
  • Rituraj Purohit


Huntington’s disorder (HD), caused by mutations of the IT-15 gene, is an autosomal genetic disease that causes the breakdown of the nerve cells in the brain. The IT-15 gene encodes the huntingtin (Htt) protein. Htt, along with its interacting partners, are involved in maintaining proper communication among neurons. Our work is based on the interaction behavior between Htt (in three polyglutamine (polyQ) states that is Htt 0Q, 17Q and 36Q) and SH3GL3 interacting protein by using computational methods. We used the HADDOCK docking platform to find out the extent of interaction between Htt polyQ models and SH3GL3. The Htt36Q (mutated) showed higher interaction than Htt17Q (native) with SH3GL3. Molecular dynamics simulation was performed to uncover the structural fluctuations of polyQ models and their complexes. RMSD, Rg, SASA, and total interaction energy graph showed significant results, where as mutant Htt showed higher fluctuations and flexibility than native Htt. The increase in the length of polyQ was found to affect the stability, flexibility, and compactness of the protein and its complex. Our research provided a propitious approach to understand the consequence of polyglutamination in Htt and its relation with HD.


Huntingtin Molecular dynamics Biological partner Polyglutamine 



We gratefully acknowledge the Bioinformatics Resources and Applications Facility (BRAF), C-DAC, Pune for providing the facilities to carry out this work.

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Chandrasekhar Gopalakrishnan
    • 1
  • Namrata Kalsi
    • 1
  • Shraddha Jethi
    • 1
  • Rituraj Purohit
    • 2
  1. 1.School of Bio Sciences and Technology (SBST)Bioinformatics Division Vellore Institute of Technology UniversityVelloreIndia
  2. 2.Division of BiotechnologyCSIR-Institute of Himalayan Bioresource TechnologyPalampurIndia

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