2.2 Selection of structural files of proteins bearing pathogenic
and benign missense mutations.
To bring the analysis to the structural level we have queried VarMap
[19], to associate each of our mutations to a protein structure
file. Structures were available in the PDB only for a fraction of the
mutations. Furthermore, as PISA database contains only 84% of all
protein PDB entries, we had to take into account 1,253 and 1,580 protein
structures to locate respectively 5,641 PMMs and 3,018 BMMs. The surface
accessibility of replaced amino acids has been calculated with POPS
software [20]. PyMOL [21] was used for molecular graphics and to
generate mutant structures by using its Mutagenesis routine; we used the
Optimize plugin for energy minimization of mutants [22].
2.3 Profiling of amino acid occurrences for pathogenic and benign
missense mutations. We have implemented a series of Python scripts,
downloadable from https://github.com [23] to collect all amino acid
replacements that occur in BMM and PMM data sets.