ANGDelmut is a web-based tool for predicting and analyzing the functional loss mechanisms of deleterious angiogenin mutations associated with amyotrophic lateral sclerosis (ALS). The ANG gene is one of the most frequently mutated genes found in ALS patients across diverse ethnic groups. Human ANG encodes a 14.1 kDa monomeric protein (ANG) that induces neovascularization, maintains physiology and health of motor neurons by inducing angiogenesis, stimulates neurite outgrowth and path-finding, protects motor neurons from hypoxia-induced death, and hence acts as a neuroprotective factor. Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS (Padhi et al. (2012) PLoS ONE; Padhi et al. (2013) Scientific Reports; Padhi et al. (2013) FEBS Letters). However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s) of ANG mutants. In light of this observation, ANGDelMut web-tool is created, which predicts whether an ANG mutation is deleterious or benign based on a series of molecular dynamics (MD) simulations and analyses (Padhi et al. (2013) F1000Research).
a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations
Angiogenin mutants and Molecular simulations
Select ANG mutation
View mRNA sequence View protein sequence
o Loss of ribonucleolytic activity
Conformational switching of His114.
Hydrogen bond interaction path mediated through Leu115.
o Loss of nuclear translocation activity
Reduction of solvent accessible surface area (SASA).
Local folding of nuclear localization signal residues 31RRR33.
Root mean square deviation (RMSD).
Amino acid Position Characteristic
Select attributes that distinguish deleterious mutations