Internal force field in selected proteins

The fuzzy oil drop model suggests that the tertiary conformation of a protein – particularly a globular one - can be likened to a spherical micelle. During the folding process, hydrophilic residues are exposed on the surface, while hydrophobic residues are retained inside the protein. The resulting hydrophobicity distribution can be mathematically modeled as a 3D Gaussian. The fuzzy oil drop model is strikingly effective in explaining the properties of type II antifreeze proteins and fast-folding proteins, as well as a vast majority of autonomous protein domains. This work aims to determine whether similar mechanisms apply to other types of nonbonding interactions. Our analysis indicates that electrostatic and van der Waals forces do not conform to the Gaussian pattern. The study involves a reference protein (titin) which shows a high agreement between the observed distribution of hydrophobicity and the theoretical (Gaussian) distribution, a selection of amyloid structures derived from the Protein Data Bank, as well as transthyretin - a protein known for its susceptibility to amyloid transformation

Different synergy in amyloids and biologically active forms of proteins

Protein structure is the result of the high synergy of all amino acids present in the protein. This synergy is the result of an overall strategy for adapting a specific protein structure. It is a compromise between two trends: The optimization of non-binding interactions and the directing of the folding process by an external force field, whose source is the water environment. The geometric parameters of the structural form of the polypeptide chain in the form of a local radius of curvature that is dependent on the orientation of adjacent peptide bond planes (result of the respective Phi and Psi rotation) allow for a comparative analysis of protein structures. Certain levels of their geometry are the criteria for comparison. In particular, they can be used to assess the differences between the structural form of biologically active proteins and their amyloid forms. On the other hand, the application of the fuzzy oil drop model allows the assessment of the role of amino acids in the construction of tertiary structure through their participation in the construction of a hydrophobic core. The combination of these two models-the geometric structure of the backbone and the determining of the participation in the construction of the tertiary structure that is applied for the comparative analysis of biologically active and amyloid forms - is presented

The structure of amyloid versus the structure of globular proteins

The issue of changing the structure of globular proteins into an amyloid form is in the focus of researchers' attention. Numerous experimental studies are carried out, and mathematical models to define the essence of amyloid transformation are sought. The present work focuses on the issue of the hydrophobic core structure in amyloids. The form of ordering the hydrophobic core in globular proteins is described by a 3D Gaussian distribution analog to the distribution of hydrophobicity in a spherical micelle. Amyloid fibril is a ribbon-like micelle made up of numerous individual chains, each representing a flat structure. The distribution of hydrophobicity within a single chain included in the fibril describes the 2D Gaussian distribution. Such a description expresses the location of polar residues on a circle with a center with a high level of hydrophobicity. The presence of this type of order in the amyloid forms available in Preotin Data Bank (PDB) (both in proto- and superfibrils) is demonstrated in the present work. In this system, it can be assumed that the amyloid transformation is a chain transition from 3D Gauss ordering to 2D Gauss ordering. This means changing the globular structure to a ribbon-like structure. This observation can provide a simple mathematical model for simulating the amyloid transformation of proteins

Alternative Hydrophobic Core in Proteins - The Effect of Specific Synergy

Proteins with a high degree of sequence similarity representing different structures provide a key to understand how protein sequence codes for 3D structure. An analysis using the fuzzy oil drop model was carried out on two pairs of proteins with different secondary structures and with high sequence identities. It has been shown that distributions of hydrophobicity for these proteins are approximated well using single 3D Gaussian function. In other words, the similar sequences fold into different 3D structures, however, alternative structures also have symmetric and monocentric hydrophobic cores. It should be noted that a significant change in the helical to beta-structured form in the N-terminal section takes places in the fragment much preceding the location of the mutated regions. It can be concluded that the final structure is the result of a complicated synergy effect in which the whole chain participates simultaneously

The status of edge strands in ferredoxin-like fold

There is an opinion in professional literature that edge-strands in β-sheet are critical to the processes of amyloid transformation. Propagation of fibrillar forms mainly takes place on the basis of β-sheet type interactions. In many proteins, the edge strands represent only a partially matched form to the β-sheet. Therefore, the edge-strand takes slightly distorted forms. The assessment of the level of arrangement can be carried out based on studying the secondary structure as well as the structure of the hydrophobic core. For this purpose, a fuzzy oil drop model was used to determine the contribution of each fragment with a specific secondary structure to the construction of the system being the effect of a certain synergy, which results in the construction of a hydrophobic core. Studying the participation of β-sheets edge fragments in the hydrophobic core construction is the subject of the current analysis. Statuses of these edge fragments in β-sheets in ferredoxin-like folds are treated as factors that disturb the symmetry of the system

Filamentous aggregates of tau proteins fulfil standard amyloid criteria provided by the fuzzy oil drop (FOD) model

Abnormal filamentous aggregates that are formed by tangled tau protein turn out to be classic amyloid fibrils, meeting all the criteria defined under the fuzzy oil drop model in the context of amyloid characterization. The model recognizes amyloids as linear structures where local hydrophobicity minima and maxima propagate in an alternating manner along the fibril’s long axis. This distribution of hydrophobicity differs greatly from the classic monocentric hydrophobic core observed in globular proteins. Rather than becoming a globule, the amyloid instead forms a ribbonlike (or cylindrical) structure

Implementation of selected statistical methods for the analysis of microarray data

W celu zrozumienia danych uzyskanych z mikromacierzy potrzebne jest zastosowanie szeregu różnych metod statystycznych. Pozwoli to na lepszą interpretacje uzyskanych wyników, odczytanie zależności wśród badanego zestawu danych oraz ilustracje uzyskanych wyników. Dlatego praca ma na celu przegląd wybranych metod statystycznych służących analizie danych uzyskiwanych w oparciu o technologię mikromacierzową oraz ich implementacje w środowisku R.In order to understand data acquired from microarrays variousstatistical methods are needed. It will allow for better interpretation ofobtained study results, finding dependencies in the data set, as well asillustrating the results. This is why this thesis focuses on selectedstatistical methods that are used in analyzing data acquired with the helpof microarray technology, as well as implementing them in the Renvironment