Amyloid as a ribbon-like micelle

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Contingency table browser : prediction of early stage protein structure

The Early Stage (ES) intermediate represents the starting structure in protein folding simulations based on the Fuzzy Oil Drop (FOD) model. The accuracy of FOD predictions is greatly dependent on the accuracy of the chosen intermediate. A suitable intermediate can be constructed using the sequence-structure relationship information contained in the so-called contingency table − this table expresses the likelihood of encountering various structural motifs for each tetrapeptide fragment in the amino acid sequence. The limited accuracy with which such structures could previously be predicted provided the motivation for a more indepth study of the contingency table itself. The Contingency Table Browser is a tool which can visualize, search and analyze the table. Our work presents possible applications of Contingency Table Browser, among them - analysis of specific protein sequences from the point of view of their structural ambiguity

Towards the design of anti-amyloid short peptide helices

A set of short peptide sequences susceptible to fibrillar aggregation produces sequneces capable of arresting elongation of amyloid fibrils. The "stop" signals are short helices customized for each individual target. Such a helix should exhibit high amphiphilicity, with differing conditions present on each side (one side should be highly hydrophilic to enable water to interact with the aggregate, while the other side must retain a local distribution of hydrophobicity which matches that of the terminal portion of the fibril). The emergence and elongation of fibrillary forms resulting from linear propagation of local hydrophobicity peaks is shown using the fuzzy oil drop model

Model of early stage intermediate in respect to its final structure

The model, describing a method of determining the structure of an early intermediate in the process of protein folding to analyze nonredundant PDB protein bases, allows determining the relationship between the sequence of tetrapeptides and their structural forms expressed by structural codes. The contingency table expressing such a relationship can be used to predict the structure of polypeptides by proposing a structural form with a precision limited to the structural code. However, by analyzing structural forms in native forms of proteins based on the fuzzy oil drop model, one can also determine the status of polypeptide chain fragments with respect to the assumptions of this model. Whether the probability distributions for both compliant and noncompliant forms were similar or whether the tetrapeptide sequences showed some differences at a level of a set of structural codes was investigated. The analysis presented here indicated that some sequences in both forms revealed differences in probability distributions expressed as a negative statistically significant correlation coefficient. This meant that the identified sections (tetrapeptides) took different forms against the fuzzy oil drop model. It may suggest that the information of the final status with respect to hydrophobic core formation is already carried by the structure of the early-stage intermediate

Why do antifreeze proteins require a solenoid?

Proteins whose presence prevents water from freezing in living organisms at temperatures below 0 C are referred to as antifreeze proteins. This group includes molecules of varying size (from 30 to over 300 aa) and variable secondary/supersecondary conformation. Some of these proteins also contain peculiar structural motifs called solenoids. We have applied the fuzzy oil drop model in the analysis of four categories of antifreeze proteins: 1 e very small proteins, i.e. helical peptides (below 40 aa); 2 e small globular proteins (40e100 aa); 3 e large globular proteins (>100 aa) and 4 e proteins containing solenoids. The FOD model suggests a mechanism by which antifreeze proteins prevent freezing. In accordance with this theory, the presence of the protein itself produces an ordering of water molecules which counteracts the formation of ice crystals. This conclusion is supported by analysis of the ordering of hydrophobic and hydrophilic residues in antifreeze proteins, revealing significant variability e from perfect adherence to the fuzzy oil drop model through structures which lack a clearly defined hydrophobic core, all the way to linear arrangement of alternating local minima and maxima propagating along the principal axis of the solenoid (much like in amyloids). The presented model e alternative with respect to the ice docking model e explains the antifreeze properties of compounds such as saccharides and fatty acids. The fuzzy oil drop model also enables differentiation between amyloids and antifreeze proteins