Prediction of Functional Loss of Human Angiogenin Mutants Associated with ALS by Molecular Dynamics Simulations

Overview

Journal Sci Rep

Specialty Science

Date 2013 Feb 9

PMID 23393617

Citations 22

Authors

Aditya K Padhi

Bhyravabhotla Jayaram

James Gomes

Affiliations

Soon will be listed here.

Abstract

Several missense mutations in the coding region of angiogenin (ANG) gene have been identified in Amyotrophic Lateral Sclerosis (ALS) patients. These mutations lead to loss of either ribonucleolytic activity or nuclear translocation activity or both of ANG (protein encoded by ANG gene) causing ALS. We present here a cohesive and comprehensive picture of the molecular origins of functional loss of all ALS associated ANG mutants, emerging via extensive molecular dynamics simulations. Our method effectively predicts that conformational change of His114 results in loss of ribonucleolytic activity and that reduction of solvent accessible surface area of nuclear localization signal residues (31)RRR(33) results in loss of nuclear translocation activity. These predictions hold true, without exception, for all ANG mutants studied and can be employed to infer whether a new ANG mutation is causative of ALS or benign ahead of experimental findings.

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