About this Research Topic
Emphasis will be on protein structural understanding, although combination of structural and sequence-based techniques will also be considered. Special emphasis will be on methods stemming from protein topology and machine learning techniques. While the focus is on computational genomics, we welcome contributions that include a combination of computational and experimental work. We include contributions pertaining to both disease and evolution of new functions. Although our primary focus is rooted in bioinformatics, we welcome reports of molecular simulations in which new insight is gained towards mutation and functionality, as well as Genome-scale Metabolic models which facilitate understanding of why a mutation does or does not contribute to disease.
We would be interested especially in new research submissions about any of the following topics:
1. Rationalization, based on protein structure (and also, optionally, systems biology) of why missense mutations are pathogenic or benign.
2. Convergent evolution towards ligand or DNA binding (e.g., pioneer transcription factors that bind specific DNA motifs, make chromatin accessible, and establish new phenotypes).
3. Domain swapping and aggregation upon mutation.
4. Molecular Dynamics or Monte Carlo simulations of mutants, which help explain experiments or make validated predictions (e.g., mutations that increase protein stability or activity).
5. Predictions and/or rationalizations of the ability to treat disease with pharmacological chaperones, based on protein structure (and, optionally, also sequence).
6. Mutational scanning for altering the activity or stability of a protein, combined with structural rationalization.
7. Underground metabolism and evolution of new or specialized functions.
Keywords: missense mutation, genetic variants, molecular evolution, protein topology, molecular dynamics, computational biology, mendelian disease
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.