Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics

We describe a combination of all-atom simulations with CABS, a well-established coarse-grained protein modeling tool, into a single multiscale protocol. The simulation method has been tested on the C-terminal beta hairpin of protein G, a model system of protein folding. After reconstructing atomistic details, conformations derived from the CABS simulation were subjected to replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb force fields in explicit solvent. Such a combination accelerates system convergence several times in comparison with all-atom simulations starting from the extended chain conformation, demonstrated by the analysis of melting curves, the number of native-like conformations as a function of time and secondary structure propagation. The results strongly suggest that the proposed multiscale method could be an efficient and accurate tool for high-resolution studies of protein folding dynamics in larger systems.Comment: 12 pages, 4 figure

Towards the high-resolution protein structure prediction. Fast refinement of reduced models with all-atom force field

<p>Abstract</p> <p>Background</p> <p>Although experimental methods for determining protein structure are providing high resolution structures, they cannot keep the pace at which amino acid sequences are resolved on the scale of entire genomes. For a considerable fraction of proteins whose structures will not be determined experimentally, computational methods can provide valuable information. The value of structural models in biological research depends critically on their quality. Development of high-accuracy computational methods that reliably generate near-experimental quality structural models is an important, unsolved problem in the protein structure modeling.</p> <p>Results</p> <p>Large sets of structural decoys have been generated using reduced conformational space protein modeling tool CABS. Subsequently, the reduced models were subject to all-atom reconstruction. Then, the resulting detailed models were energy-minimized using state-of-the-art all-atom force field, assuming fixed positions of the alpha carbons. It has been shown that a very short minimization leads to the proper ranking of the quality of the models (distance from the native structure), when the all-atom energy is used as the ranking criterion. Additionally, we performed test on medium and low accuracy decoys built via classical methods of comparative modeling. The test placed our model evaluation procedure among the state-of-the-art protein model assessment methods.</p> <p>Conclusion</p> <p>These test computations show that a large scale high resolution protein structure prediction is possible, not only for small but also for large protein domains, and that it should be based on a hierarchical approach to the modeling protocol. We employed Molecular Mechanics with fixed alpha carbons to rank-order the all-atom models built on the scaffolds of the reduced models. Our tests show that a physic-based approach, usually considered computationally too demanding for large-scale applications, can be effectively used in such studies.</p

Thermo-Oxidation of Phytosterol Molecules in Rapeseed Oil during Heating: The Impact of Unsaturation Level of the Oil

Phytosterols are naturally occurring substances in foods of plant origin that have positive effects on the human body. Their consumption can reduce the level of low density lipoprotein (LDL) cholesterol. The presence of unsaturated bonds in their structure leads to their oxidation during production, storage, and thermal processes. The aim of the study was to determine how the degree of unsaturation of rapeseed oil affects the oxidation of phytosterols in oil during 48 h of heating. In all not-heated oils, the dominant groups of oxyphytosterols were 7α- and 7β-hydroxy sterols. During 48 h of heating, the rapid decrease of phytosterols’ levels and the increase of the content of oxyphytosterols were observed. The main dominant group in heated samples was hydroxy and epoxy sterols. Despite differences in fatty acid composition and content and composition of single phytosterols in unheated oils samples, the total content of oxyphytosterols after finishing of heating was on a similar level for each of the tested oils. This showed that the fatty acid composition of oil is not the only factor that affects the oxidation of phytosterols in foods during heating

Degradation of Tocopherol Molecules and Its Impact on the Polymerization of Triacylglycerols during Heat Treatment of Oil

The aim of the study was to analyze the influence of the surface area to volume ratio of pressed and refined rapeseed oils on the changes in tocopherol content and polymerization of triacylglycerols during heating. In the study the pressed and refined rapeseed oil was heated at 170 &deg;C, during 6, 12, and 18 h with three different surface area to volume (s/v) ratios (0.378, 0.189, and 0.126 cm&minus;1). During heating, a decrease in tocopherols and increases in dimers, trimers, and oligomers of triacylglycerols were observed. However, the changes were dependent on the surface area to volume ratio used, type of oil and time of heating. The biggest changes were observed in oil with the biggest s/v ratio (0.378 cm&minus;1), and the lowest when the s/v ratio was 0.126 cm&minus;1. The pressed oil was characterized by faster degradation of tocopherols and slower increase of triacylglycerol polymer levels compared to refined oil

Influence of storage time on peroxide and anisidine value changes of fried and frozen potato products

Celem badań było określenie wpływu przechowywania, na jakość mrożonych ziemniaczanych produktów smażonych. W czasie 15 miesięcy przechowywano 21 mrożonych produktów ziemniaczanych: frytki ziemniaczane (14), cząstki i talarki (5) oraz kuleczki ziemniaczane (2) wyprodukowane przez trzech różnych producentów. Próby do analiz pobierano po 6, 12 i 15 miesiącach przechowywania. Przechowywanie odbywało się w dwóch odrębnych opakowaniach stanowiących dwa powtórzenia próby w temperaturze -21°C. W produktach określono zmiany liczby nadtlenkowej i anizydynowej. W próbach bezpośrednio po zakupie liczba nadtlenkowa wahała się od 2,54 do 11,56 mEq O2/1 kg, a liczba anizydynowa od 17,09 do 89,15. Oba wyróżniki były najczęściej związane z rodzajem tłuszczu wykorzystywanego do produkcji (olej słonecznikowy, olej palmowy). W czasie przechowywania obserwowano wahania obu wyróżników, jednakże po jego zakończeniu w większości prób stwierdzono wzrost zarówno liczby nadtlenkowej jak i liczby anizydynowej. Po zakończeniu przechowywania liczba nadtlenkowa wahała się od 4,56 do 18,06 mEq O2/1 kg, natomiast liczba anizydynowa w granicach od 28,36 do 122,84.The aim of the study was to determine the effect of long-term storage on the quality of fried and frozen potato products. The 21 frozen potato products: French fries (14), potato wedges and potato slices (5), potato balls (2) were purchased from three different manufacturers and were stored at -21°C for 15 months. The samples for analysis were taken after 6, 12 and 15 months of storage. Storage was carried out for two different product packages representing two replicates of the same sample (package I and II). In the analyzed products the changes of peroxide and anisidine values were determined. Both peroxide and anisidine values of the samples analyzed immediately after the purchase varied within a very wide range from 2.54 to 11.56 mEq O2/1 kg and from 17.09 to 89.15, respectively. It was most commonly associated with the type of oil used for industrial frying of products (sunflower or palm oil). During 15-month storage the increase of the peroxide and anisidine values in all analyzed samples was observed. The final levels of peroxide and anisidine values varied from 4.56 to 18.06 mEq O2/1 kg and from 28.36 to 122.84, respectively

Nutritional Quality and Oxidative Stability during Thermal Processing of Cold-Pressed Oil Blends with 5:1 Ratio of &omega;6/&omega;3 Fatty Acids

The growing awareness of consumers means that new products are sought after, which, apart from meeting the basic demand for macronutrients and energy, will have a positive impact on our health. This article is a report on the characteristics of the new oil blends with a nutritious &omega;6/&omega;3 fatty acid ratio (5:1), as well as the heat treatment effect on the nutritional value and stability of the oils. Prepared oil blends were heated at 170 and 200 &deg;C. The fatty acid composition and the changes in tocochromanols content during heating were analyzed, as well as the formation process of polar compounds and triacylglycerol polymers. During heating the highest loss of tocochromanols was characteristic of &alpha;-tocopherol and &alpha;-tocotrienol. The total content of tocopherols after heating was reduced to 1&ndash;6% of the original content in the unheated oil blends. The exception was the blend of oil with wheat germ oil, in which a high content of all tocopherols was observed in unheated and heated samples. The content of the polar fraction during heating increased on average 1.9 and 3.1 times in the samples heated at 170 and 200 &deg;C, respectively, compared to the unheated oils. The level of the polar fraction was related to the high content of tocopherols or the presence of tocopherols and tocotrienols in the heated sample. The polymerization of triacylglycerols led mainly to the formation of triacylglycerol dimers. Trimers were observed in a small number of heated samples, especially those heated at 200 &deg;C. Regardless of the changes in heated oils, none of the prepared blends exceeded the limit of the polar fraction content, maintaining the programmed ratio of &omega;6 to &omega;3 acids. The principal component analysis (PCA) used to define the clusters showed a large variety of unheated and heated samples. An outlier in all clusters was a blend of oil with wheat germ oil. In these samples, the degradation of tocopherols molecules and the increase of triacylglycerol polymers and the polar fraction content were the slowest

Nutritional Quality and Oxidative Stability during Thermal Processing of Cold-Pressed Oil Blends with 5:1 Ratio of ω6/ω3 Fatty Acids

The growing awareness of consumers means that new products are sought after, which, apart from meeting the basic demand for macronutrients and energy, will have a positive impact on our health. This article is a report on the characteristics of the new oil blends with a nutritious ω6/ω3 fatty acid ratio (5:1), as well as the heat treatment effect on the nutritional value and stability of the oils. Prepared oil blends were heated at 170 and 200 °C. The fatty acid composition and the changes in tocochromanols content during heating were analyzed, as well as the formation process of polar compounds and triacylglycerol polymers. During heating the highest loss of tocochromanols was characteristic of α-tocopherol and α-tocotrienol. The total content of tocopherols after heating was reduced to 1–6% of the original content in the unheated oil blends. The exception was the blend of oil with wheat germ oil, in which a high content of all tocopherols was observed in unheated and heated samples. The content of the polar fraction during heating increased on average 1.9 and 3.1 times in the samples heated at 170 and 200 °C, respectively, compared to the unheated oils. The level of the polar fraction was related to the high content of tocopherols or the presence of tocopherols and tocotrienols in the heated sample. The polymerization of triacylglycerols led mainly to the formation of triacylglycerol dimers. Trimers were observed in a small number of heated samples, especially those heated at 200 °C. Regardless of the changes in heated oils, none of the prepared blends exceeded the limit of the polar fraction content, maintaining the programmed ratio of ω6 to ω3 acids. The principal component analysis (PCA) used to define the clusters showed a large variety of unheated and heated samples. An outlier in all clusters was a blend of oil with wheat germ oil. In these samples, the degradation of tocopherols molecules and the increase of triacylglycerol polymers and the polar fraction content were the slowest

Denatured proteins and early folding intermediates simulated in a reduced conformational space

Conformations of globular proteins in the denatured state were studied using a high-resolution lattice model of proteins and Monte Carlo dynamics. The model assumes a united-atom and high-coordination lattice representation of the polypeptide conformational space. The force field of the model mimics the short-range protein-like conformational stiffness, hydrophobic interactions of the side chains and the main-chain hydrogen bonds. Two types of approximations for the short-range interactions were compared: simple statistical potentials and knowledge-based protein-specific potentials derived from the sequence-structure compatibility of short fragments of protein chains. Model proteins in the denatured state are relatively compact, although the majority of the sampled conformations are globally different from the native fold. At the same time short protein fragments are mostly native-like. Thus, the denatured state of the model proteins has several features of the molten globule state observed experimentally. Statistical potentials induce native-like conformational propensities in the denatured state, especially for the fragments located in the core of folded proteins. Knowledge-based protein-specific potentials increase only slightly the level of similarity to the native conformations, in spite of their qualitatively higher specificity in the native structures. For a few cases, where fairly accurate experimental data exist, the simulation results are in semiquantitative agreement with the physical picture revealed by the experiments. This shows that the model studied in this work could be used efficiently in computational studies of protein dynamics in the denatured state, and consequently for studies of protein folding pathways, i.e. not only for the modeling of folded structures, as it was shown in previous studies. The results of the present studies also provide a new insight into the explanation of the Levinthal's paradox