caa a22 4500 606234659 CHVBK 20210128101238.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2462-7 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2462-7 Computational investigation of molecular mechanism and neuropathological implications in Huntington disease [Elektronische Daten] [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. Springer Science+Business Media New York, 2015 Huntingtin nationallicence Molecular dynamics nationallicence Biological partner nationallicence Polyglutamine nationallicence Gopalakrishnan Chandrasekhar School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Kalsi Namrata School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Jethi Shraddha School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut Purohit Rituraj Division of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 1-11 0300-8177 409:1-2<1 2015 409 11010 https://doi.org/10.1007/s11010-015-2462-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2462-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gopalakrishnan Chandrasekhar School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 700 1- Kalsi Namrata School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 700 1- Jethi Shraddha School of Bio Sciences and Technology (SBST), Bioinformatics Division Vellore Institute of Technology University, 632014, Vellore, Tamil Nadu, India aut NATIONALLICENCE 700 1- Purohit Rituraj Division of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur, Himachal Pradesh, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 1-11 0300-8177 409:1-2<1 2015 409 11010