文章基本信息

标题：Prediction of Functional Loss of Human Angiogenin Mutants Associated with ALS by Molecular Dynamics Simulations
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作者：Aditya K. Padhi ; Bhyravabhotla Jayaram ; James Gomes 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2013
卷号：3
DOI：10.1038/srep01225
出版社：Springer Nature
摘要：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 ³¹RRR³³ 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.