Living systems rely on coordinated molecular interactions, especially those related to gene expression and protein activity. The Unfolded Protein Response is a crucial mechanism in eukaryotic cells, activated when unfolded proteins exceed a critical threshold. It maintains cell homeostasis by enhancing protein folding, initiating quality control, and activating degradation pathways when damage is irreversible. This response functions as a dynamic signaling network, with proteins as nodes and their interactions as edges. We analyze these protein-protein networks across different organisms to understand their intricate intra-cellular interactions and behaviors. In this work, analyzing twelve organisms, we assess how fundamental measures in network theory can individuate seed-proteins and specific pathways across organisms. We employ network robustness to evaluate and compare the strength of the investigated PPI networks, and the structural controllability of complex networks to find and compare the sets of driver nodes necessary to control the overall networks. We find that network measures are related to phylogenetics, and advanced network methods can identify main pathways of significance in the complete Unfolded Protein Response mechanism.
Extended Experimental Inferential Structure Determination Method for Evaluating the Structural Ensembles of Disordered Protein States
表征具有内在或未折叠状态的蛋白质包括结构生物学中的新前沿，需要表征多样和动态的结构集合。我们介绍了一个全面的贝叶斯框架，扩展实验推断结构确定（X-EISD）方法，该方法通过考虑广泛的实验数据和结构的反算模型的不确定性来计算蛋白质结构系综的最大对数似然，包括NMR化学位移，J-耦合，核奥弗豪泽效应，顺磁弛豫增强，残余偶极耦合，和流体动力学半径，单分子荧光Förster共振能量转移效率和小角X射线散射强度曲线。我们将X-EISD应用于drkN SH 3展开状态域，并表明某些实验数据类型比其他类型更有影响力，既消除了结构系综模型，同时也找到了同样可能的无序系综，这些系综具有替代结构特性，将刺激进一步的实验来区分它们。
The thermodynamics of protein aggregation reactions may underpin the enhanced metabolic efficiency associated with heterosis, some balancing selection, and the evolution of ploidy levels
Role of the dihedral angle potential in the nucleation pathway of protein folding
提出了蛋白质折叠成核机理的动力学模型。蛋白质被建模为由具有相等恒定键长和键角的疏水性和亲水性珠粒组成的杂聚物。杂聚物的总能量由非连接珠的排斥/吸引相互作用和所涉及的二面角的贡献决定。它们的参数可以严格定义，不像以前模型的基础是一簇蛋白质残基的不明确的表面张力。作为该模型的一个重要思想，二面角势，其中所选择的珠参与平均所有可能的配置的相邻珠沿蛋白质链。由此产生的平均二面角潜力的残留物是恒定的足够远的集群，但单调增加的距离降低低于阈值。其中残基执行混沌运动的簇周围的总体势是平均二面角势和成对势的组合。作为与簇的距离的函数，它具有双阱形状。内孔中的残基被认为属于簇（蛋白质的折叠部分），而外孔中的残基被视为属于蛋白质的未折叠（尽管是紧凑的）部分。双井形状的潜力周围的集群允许一个确定其发射和吸收率，通过使用第一次通过时间分析和发展的自洽动力学理论的成核机制的蛋白质折叠。对一个含有2500个残基的蛋白质进行数值计算，其残基在天然状态下的扩散系数在10^{-6} cm ^2/s到10^{-8} cm ^2/s之间，预测折叠时间在几秒到几百秒之间。
