title: Relationship between population of the fibril-prone conformation in the monomeric state and oligomer formation times of peptides: insights from all-atom simulations.
abstract: Despite much progress in understanding the aggregation process of biomolecules, the factors that govern its rates have not been fully understood. This problem is of particular importance since many conformational diseases such as Alzheimer, Parkinson, and type-II diabetes are associated with the protein oligomerization. Having performed all-atom simulations with explicit water and various force fields for two short peptides KFFE and NNQQ, we show that their oligomer formation times are strongly correlated with the population of the fibril-prone conformation in the monomeric state. The larger the population the faster the aggregation process. Our result not only suggests that this quantity plays a key role in the self-assembly of polypeptide chains but also opens a new way to understand the fibrillogenesis of biomolecules at the monomeric level. The nature of oligomer ordering of NNQQ is studied in detail.
authors.affiliation: Institute for Computational Science and Technology, 6 Quarter, Linh Trung Ward, Thu Duc District, Ho Chi Minh City, Vietnam.
authors.forename: Hoang Bao
authors.initials: HB
authors.lastname: Nam
authors.forename: Maksim
authors.initials: M
authors.lastname: Kouza
authors.forename: Hoang
authors.initials: H
authors.lastname: Zung
authors.forename: Mai Suan
authors.initials: MS
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000737:chemistry; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011328:Prions / Q000737:chemistry; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D013816:Thermodynamics
chemical_list: D005656:Fungal Proteins; D010446:Peptide Fragments; D010455:Peptides; D011328:Prions