Banavar Jayanth R, Giacometti Achille, Hoang Trinh X, Maritan Amos, Škrbić Tatjana
Department of Physics and Institute for Fundamental Science, University of Oregon, Eugene, Oregon, USA.
Ca' Foscari University of Venice, Department of Molecular Sciences and Nanosystems, Venice, Italy.
Proteins. 2025 Jan;93(1):145-159. doi: 10.1002/prot.26567. Epub 2023 Aug 10.
We present a model, based on symmetry and geometry, for proteins. Using elementary ideas from mathematics and physics, we derive the geometries of discrete helices and sheets. We postulate a compatible solvent-mediated emergent pairwise attraction that assembles these building blocks, while respecting their individual symmetries. Instead of seeking to mimic the complexity of proteins, we look for a simple abstraction of reality that yet captures the essence of proteins. We employ analytic calculations and detailed Monte Carlo simulations to explore some consequences of our theory. The predictions of our approach are in accord with experimental data. Our framework provides a rationalization for understanding the common characteristics of proteins. Our results show that the free energy landscape of a globular protein is pre-sculpted at the backbone level, sequences and functionalities evolve in the fixed backdrop of the folds determined by geometry and symmetry, and that protein structures are unique in being simultaneously characterized by stability, diversity, and sensitivity.
我们提出了一个基于对称性和几何学的蛋白质模型。运用数学和物理学的基本概念，我们推导出了离散螺旋和片层的几何结构。我们假定存在一种由溶剂介导的、兼容的、能组装这些构建模块的成对吸引力，同时尊重它们各自的对称性。我们并非试图模仿蛋白质的复杂性，而是寻求对现实的一种简单抽象，这种抽象却能抓住蛋白质的本质。我们采用解析计算和详细的蒙特卡罗模拟来探究我们理论的一些结果。我们方法的预测结果与实验数据相符。我们的框架为理解蛋白质的共同特征提供了一种合理化解释。我们的结果表明，球状蛋白质的自由能景观在主链层面就已预先塑造，序列和功能在由几何结构和对称性决定的折叠的固定背景中演化，并且蛋白质结构的独特之处在于同时具有稳定性、多样性和敏感性。
