Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2047793 | FEBS Letters | 2013 | 5 Pages |
•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.