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Why do we need to use both entropy and p-value cutoffs in predicting important residues?

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Why do we need to use both entropy and p-value cutoffs in predicting important residues?

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A. Two cutoffs are needed because small number of residues have low p-value, but relatively high entropy. We noticed this a while ago and always wanted to go after these residues as they can be variable (higher entropy) surface residues that are less variable than expected indicating some involvement in binding. These residues are not truly CoC, so we need to filter them out by the cutoff on entropy.

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