Current Challenges and Limitations in the Studies of Intrinsically Disordered Proteins in Neurodegenerative Diseases by Computer Simulations

• Published in: Current Alzheimer research Vol. 17; no. 9; p. 805
• Main Authors: Akbayrak, Ibrahim Y, Caglayan, Sule I, Ozcan, Zilan, Uversky, Vladimir N, Coskuner-Weber, Orkid
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2020
• Subjects: amyloid-β; neurodegenerative diseases; computer simulations; Alzheimer's disease; intrinsically disordered proteins; α-synuclein
• ISSN: 1875-5828
• DOI: 10.2174/1567205017666201109094908

Experiments face challenges in the analysis of intrinsically disordered proteins in solution due to fast conformational changes and enhanced aggregation propensity. Computational studies complement experiments, being widely used in the analyses of intrinsically disordered proteins, especially those positioned at the centers of neurodegenerative diseases. However, recent investigations - including our own - revealed that computer simulations face significant challenges and limitations themselves. In this review, we introduced and discussed some of the scientific challenges and limitations of computational studies conducted on intrinsically disordered proteins. We also outlined the importance of future developments in the areas of computational chemistry and computational physics that would be needed for generating more accurate data for intrinsically disordered proteins from computer simulations. Additional theoretical strategies that can be developed are discussed herein.