title: The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function.
abstract: In this paper we show that the fuzzy oil drop model represents a general framework for describing the generation of hydrophobic cores in proteins and thus provides insight into the influence of the water environment upon protein structure and stability. The model has been successfully applied in the study of a wide range of proteins, however this paper focuses specifically on domains representing immunoglobulin-like folds. Here we provide evidence that immunoglobulin-like domains, despite being structurally similar, differ with respect to their participation in the generation of hydrophobic core. It is shown that β-structural fragments in β-barrels participate in hydrophobic core formation in a highly differentiated manner. Quantitatively measured participation in core formation helps explain the variable stability of proteins and is shown to be related to their biological properties. This also includes the known tendency of immunoglobulin domains to form amyloids, as shown using transthyretin to reveal the clear relation between amyloidogenic properties and structural characteristics based on the fuzzy oil drop model.
authors.affiliation: Department of Bioinformatics and Telemedicine - Jagiellonian University - Medical College, Krakow, Poland; Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Banach
authors.affiliation: Chair of Medical Chemistry - Jagiellonian University - Medical College, Krakow, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Konieczny
authors.affiliation: Department of Bioinformatics and Telemedicine - Jagiellonian University - Medical College, Krakow, Poland. Electronic address: myroterm@cyf-kr.edu.pl.
authors.forename: Irena
authors.initials: I
authors.lastname: Roterman
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004777:Environment; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D051379:Mice; D008962:Models, Theoretical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000502:physiology*; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
chemical_list: D007140:Immunoglobulin Fab Fragments; D011506:Proteins; D014867:Water
keywords: Amyloidosis; Hydrophobic core; Immunoglobulin-like fold; Thansthytetin; Water environment