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Background: Coevolution within a protein family is often predicted usingstatistics that measure the degree of covariation between positions in theprotein sequence. Mutual Information is a measure of dependence between tworandom variables that has been used extensively to predict intra-proteincoevolution.  Results: Here we provide an algorithm for the efficient calculation of MutualInformation within a protein family. The algorithm uses linked lists which aredirectly accessed by a pointer array. The linked list allows efficient storageof sparse count data caused by protein conservation. The direct access array ofpointers prevents the linked list from being traversed each time it ismodified.  Conclusions: This algorithm is implemented in the software MIpToolset, butcould also be easily implemented in other Mutual Information based standalonesoftware or web servers. The current implementation in the MIpToolset has beencritical in large-scale protein family analysis and real-time coevolutioncalculations during alignment editing and curation.  The MIpToolset is available at: https://sourceforge.net/projects/miptoolset/

The MIp Toolset: an efficient algorithm for calculating Mutual Information in protein alignments