Modeltest 3.7 [ 68] was run for all data sets (individual and combined) to select a model of sequence evolution.
To select a model of protein evolution, ProtTest needs to be run, and the selected model needs to be implemented in the tree building.
ProtTest [ 78] was used to select a model of molecular evolution and MrBayes [ 79] was used to create a Bayesian estimation of the phylogeny.
We selected a model of gastric GIST to obtain a balanced set of tumours with mutations in either KIT or PDGFRA [ 21].
For our experiment, we selected a model of minimally-invasive fracture of the tibia diaphysis with subsequent intramedullary osteosynthesis in rabbits as recommended by Sachno [ 16].
We then used the Akaike information criterion to allow each orthologous gene to select a model of protein evolution (see methods).
For each locus, we selected a model of evolution using the software PHYML [ 38] and its R interface provided by ape [ 18, 19].
To fully utilize these methods, it is also important to select a model of evolution with an appropriate level of complexity for the dataset by making use of model selection procedures, e.g. as in the ModelTest software (Posada and Crandall, 1998).
To select a model out of the top scoring docked complexes reported by GRAMM-X, we calculated the binding energy on the generated complexes removing intraclashes (using the strongest van der Waals parameters) with FoldX [34].
