Deciphering principles of nucleosome interactions and impact of cancer-associated mutations from comprehensive interaction network analysis.

Nucleosomes represent hubs in chromatin organization and gene regulation and interact with a plethora of chromatin factors through different modes. In addition, alterations in histone proteins such as cancer mutations and post-translational modifications have profound effects on histone/nucleosome interactions. To elucidate the principles of histone interactions and the effects of those alterations, we developed histone interactomes for comprehensive mapping of histone-histone interactions (HHIs), histone-DNA interactions (HDIs), histone-partner interactions (HPIs) and DNA-partner interactions (DPIs) of 37 organisms, which contains a total of 3808 HPIs from 2544 binding proteins and 339 HHIs, 100 HDIs and 142 DPIs across 110 histone variants. With the developed networks, we explored histone interactions at different levels of granularities (protein-, domain- and residue-level) and performed systematic analysis on histone interactions at a large scale. Our analyses have characterized the preferred binding hotspots on both nucleosomal/linker DNA and histone octamer and unraveled diverse binding modes between nucleosome and different classes of binding partners. Last, to understand the impact of histone cancer-associated mutations on histone/nucleosome interactions, we complied one comprehensive cancer mutation dataset including 7940 cancer-associated histone mutations and further mapped those mutations onto 419,125 histone interactions at the residue level. Our quantitative analyses point to histone cancer-associated mutations' strongly disruptive effects on HHIs, HDIs and HPIs. We have further predicted 57 recurrent histone cancer mutations that have large effects on histone/nucleosome interactions and may have driver status in oncogenesis.

Bound ion effects: Using machine learning method to study the kinesin Ncd's binding with microtubule.

Drosophila Ncd proteins are motor proteins that play important roles in spindle organization. Ncd and the tubulin dimer are highly charged. Thus, it is crucial to investigate Ncd-tubulin dimer interactions in the presence of ions, especially ions that are bound or restricted at the Ncd-tubulin dimer binding interfaces. To consider the ion effects, widely used implicit solvent models treat ions implicitly in the continuous solvent environment without focusing on the individual ions' effects. But highly charged biomolecules such as the Ncd and tubulin dimer may capture some ions at highly charged regions as bound ions. Such bound ions are restricted to their binding sites; thus, they can be treated as part of the biomolecules. By applying multiscale computational methods, including the machine-learning-based Hybridizing Ions Treatment-2 program, molecular dynamics simulations, DelPhi, and DelPhiForce, we studied the interaction between the Ncd motor domain and the tubulin dimer using a hybrid solvent model, which considers the bound ions explicitly and the other ions implicitly in the solvent environment. To identify the importance of treating bound ions explicitly, we also performed calculations using the implicit solvent model without considering the individual bound ions. We found that the calculations of the electrostatic features differ significantly between those of the hybrid solvent model and the pure implicit solvent model. The analyses show that treating bound ions at highly charged regions explicitly is crucial for electrostatic calculations. This work proposes a machine-learning-based approach to handle the bound ions using the hybrid solvent model. Such an approach is not only capable of handling kinesin-tubulin complexes but is also appropriate for other highly charged biomolecules, such as DNA/RNA, viral capsid proteins, etc.

Studying the Role of Potato Powder on the Physicochemical Properties and Dough Characteristics of Wheat Flour.

Potato flour (PF) is rich in health-promoting compounds that can improve the nutritional benefits of food products after blending with wheat flour. However, the incorporation of PF may influence the processing characteristics of mixed powders and the quality properties of products. In this study, the physicochemical properties, processing characteristics, and structures of mixed powders and their corresponding doughs with different PF content (0%, 10%, 20%, 30%, 40%, 60%, 80%, and 100%) were investigated. The addition of PF dramatically increased the fiber content from 0.09 to 1.10 g·kg-1 but diluted the protein in wheat flour. The peak and final viscosity of mixed powders decreased (from 5111.00 to 1806.33 cP and 5195.33 to 2135.33 cP, respectively) with an increase in PF fraction. The incorporation of PF significantly increased gelatinization temperature. The rapidly digestible starch decreased from 30.48% to 19.67%, and resistant starch increased from 16.93% to 41.84% when the PF content increased from 0% to 100%. The water absorption, stability time, and development time decreased with an increase in PF levels. The G' and G″ of the dough decreased as the addition amount of PF increased, while tan δ presented a complex change tendency. Due to the decrease in protein content in the mixed powders, the addition of PF in wheat flour notably decreased the Hm values of doughs and total carbon dioxide volume produced during fermentation. Additionally, the SH and S-S contents decreased with an increase in PF fraction. Scanning electron microscopy results showed that when the PF content reached up to 80%, a poor and discontinuous gluten framework was formed in the dough. Results showed that PF affected the processing characteristics and gluten structures of wheat dough and was related to the interaction or competition for water molecules between protein and starch, as well as potato starch and wheat starch. Thus, the results of the present study can provide insights into the optimal level of addition of PF during the development of potato-based food products.