title: Computational approaches to understanding protein aggregation in neurodegeneration.
abstract: The generation of toxic non-native protein conformers has emerged as a unifying thread among disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Atomic-level detail regarding dynamical changes that facilitate protein aggregation, as well as the structural features of large-scale ordered aggregates and soluble non-native oligomers, would contribute significantly to current understanding of these complex phenomena and offer potential strategies for inhibiting formation of cytotoxic species. However, experimental limitations often preclude the acquisition of high-resolution structural and mechanistic information for aggregating systems. Computational methods, particularly those combine both all-atom and coarse-grained simulations to cover a wide range of time and length scales, have thus emerged as crucial tools for investigating protein aggregation. Here we review the current state of computational methodology for the study of protein self-assembly, with a focus on the application of these methods toward understanding of protein aggregates in human neurodegenerative disorders.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Redler
authors.forename: David
authors.initials: D
authors.lastname: Shirvanyants
authors.forename: Onur
authors.initials: O
authors.lastname: Dagliyan
authors.forename: Feng
authors.initials: F
authors.lastname: Ding
authors.forename: Doo Nam
authors.initials: DN
authors.lastname: Kim
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kota
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Proctor
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Arpit
authors.initials: A
authors.lastname: Tandon
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D066329:Protein Aggregates; D017510:Protein Folding
chemical_list: D066329:Protein Aggregates
keywords: molecular dynamics; neurodegeneration; protein aggregation; protein folding