Grantham score
The Grantham score attempts to predict the distance between two amino acids, in an evolutionary sense. A lower Grantham score reflects less evolutionary distance. A higher Grantham score reflects a greater evolutionary distance. Higher Grantham scores are considered more deleterious:
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The more distant two amino acids are, the less likely the amino acids are to be substituted with one another.
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The more distant two amino acids are, the more damaging is their substitution.
The distance scores published by Grantham range from 5 to 215. A substitution of isoleucine for leucine, or of leucine for isoleucine, has a score of 5 (and is predicted to be tolerated). A substitution cysteine for tryptophan, or of tryptophan for cysteine, has a score of 215. Any variation involving cysteine has a high or very high Grantham score (and is predicted to be deleterious).
For more information on Grantham scores, see the following sites:
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Abstract for Amino acid difference formula to help explain protein evolution.
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Article for Grantham R. "Amino acid difference formula to help explain protein evolution", Science. 1974 Sep 6;185(4154):862-4.