Fast prediction of deleterious angiogenin mutations causing amyotrophic lateral sclerosis

• Functional loss mechanisms of angiogenin mutants causing ALS are poorly understood.
• Conformational switching of His114 causes loss of ribonucleolytic activity.
• Local folding of 31RRR33 residues results in loss of nuclear translocation activity.
• Hydrogen bond interactions correlate with loss of ribonucleolytic activity.
• Deleterious angiogenin mutations causing ALS can be predicted quickly.

Certain single nucleotide polymorphisms causing missense mutations in angiogenin result in its loss-of-function and onset of amyotrophic lateral sclerosis (ALS). Although several such associations are reported across diverse ethnic groups, no method is available for predicting if a new mutation is deleterious. We present here a fast molecular dynamics based method for determining the mechanisms of functional loss caused by mutations, and attributes to ascertain whether a mutation causes ALS.