Single amino acid mutations, (substitutions, insertions, or deletions) in proteins can vary in effect from negligible to complete loss of function but such effects are not generally predictable. It is generally thought that a deletion is more disruptive to the structure, and thereby the function, of a protein since the gap created must be closed in the folded conformation. Such deletions are widely observed in nature and are often detrimental to the activity and stability of the enzymes, resulting in diseases such as cancer, cystic fibrosis, or osteogenesis imperfecta. Using a set of amino acid deletions from ricin, we have developed an algorithm to model the perturbed structure of deletion mutants and predict their activity. Preliminary results show that metrics such as distortion of the active site, formation of hydrogen bonding networks, and steric clashes between the ligand and the mutant protein can be used to predict the activity in the mutant proteins. The ability to predict the activity of enzyme mutants has implications for engineering new proteins and understanding the molecular basis of disease.

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