Molecular dynamics simulations for genetic interpretation in protein coding regions: where we are, where to go and when.

Molecular dynamics simulations for genetic interpretation in protein coding regions: where we are, where to go and when. Brief Bioinform. 2019 Dec 08;: Authors: Galano-Frutos JJ, García-Cebollada H, Sancho J Abstract The increasing ease with which massive genetic information can be obtained from patients or healthy individuals has stimulated the development of interpretive bioinformatics tools as aids in clinical practice. Most such tools analyze evolutionary information and simple physical-chemical properties to predict whether replacement of one amino acid residue with another will be tolerated or cause disease. Those approaches achieve up to 80-85% accuracy as binary classifiers (neutral/pathogenic). As such accuracy is insufficient for medical decision to be based on, and it does not appear to be increasing, more precise methods, such as full-atom molecular dynamics (MD) simulations in explicit solvent, are also discussed. Then, to describe the goal of interpreting human genetic variations at large scale through MD simulations, we restrictively refer to all possible protein variants carrying single-amino-acid substitutions arising from single-nucleotide variations as the human variome. We calculate its size and develop a simple model that allows calculating the simulation time needed to have a 0.99 probability of observing unfolding events of any unstable variant. The knowledge of that time enables performing a binary classifica...
Source: Briefings in Bioinformatics - Category: Bioinformatics Authors: Tags: Brief Bioinform Source Type: research