De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.

从头开始设计和构建可预测在离散构象状态之间切换的刺激应答蛋白装配体，在生物分子设计中仍然是必不可少但极具挑战性的目标。我们先前报道了通过二硫键相互作用而自组装的二维蛋白质蛋白质晶格，这赋予了它们独特的能力，可以进行连贯的构象变化而不会失去结晶顺序。在这里，我们进行了全原子分子动力学模拟，绘制了这些晶格的自由能图，通过电子显微镜的广泛结构表征验证了该图，并确定其主要受溶剂重组熵的支配。