Back to catalogue >>

Reference: Stone E.A., Sidow A. Physicochemical constraint violation by missense substitution mediates impairment of protein function and disease severity. Genome Research (2005) 15 978-986.
Hosted: The software was developed by the Sidow Lab, Stanford Medical School, and is available to download and run locally. (http://mendel.stanford.edu/SidowLab/downloads/MAPP/index.html)

Only available for download and running locally.

Summary:
MAPP predictions are based on assessment of the physicochemical variation in each column of a sequence alignment.

Methodology:
• The evolutionary relationships between the sequences in the alignment are calculated and weights are applied to each sequence to control for the phylogenetic correlation.
• Each of the 20 possible amino acids per alignment column is represented by the sum of the weights of those sequences carrying the amino acid at that position in the alignment.
• Scores of physicochemical properties such as polarity, volume and hydropathy are applied to the column summary to capture the variation.
• Mean and variance scores of each physicochemical property are then calculated.
• For every possible variant, the deviation from each property is calculated and converted to a single score representing the violation of constraint.

Input:
The user must download the software and run it locally. MAPP needs a multiple sequence alignment and a phylogenetic tree detailing the evolutionary distance between these species.