I am working on Parkinson disease causing protein PINK1, I am focusing on 26 disease causing variants for parkinson. These variants are reported here.
There is no PDB structure for PINK1, thus I predicted it using I-Tasser. I used this structure for homology modelling through modeller. By inducing the mutation at the specific site for each variant in the sequence of PINK1, I predicted 26 structures for all the variants. The protein sequence was obtained from ensemble.
But there is no significant change in the structure of PINK1 for wild type and mutated proteins. (RMSD values below 0.4 were considered insignificant).
If there is not significant change in structure then what could be the possible mechanism through which these variants are contributing to Parkinson disease?