Our client is screening a patient‘s genome for genetic variants that are likely linked to diseases or aging. Personalised treatments are developed and tested, e.g., on cell lines derived from the patient.
Rare genetic variants may have an unknown effect, so- called “variants of unknown significance“ (VUS). The goal of this project was to study the effect of a particular VUS in a fibrous protein on the protein‘s structure and stability.
Evaluating the effect of the mutation with several established effect prediction algorithms.
Assessing the conservation of the residue and its context in homologs in human, mammals, and other species.
Performing a Molecular Dynamics (MD) simulation on the wild type and the mutant structure.
Position and context are highly conserved in homologs. Amino acid substitution is generally tolerated biochemically and observed in (unrelated) proteins.
The stability of the wild type in silico mutated structure was tested in a 100 ns Molecular Dynamics simulation.
Wild type and mutant structures remain stable throughout the MD simulation. Importances is still likely due to conservation.