We introduced a small molecular “inducing ligand” strategy to crystallize proteins via dual noncovalent interactions. Here we demonstrate that the variant protein-packing frameworks of concanavalin A (ConA) binding with ligands are controlled by different crystallization methods. Besides, the protein crystalline frameworks are also controlled by small-molecule inducing ligands RnM (n = 1–5), which varies in the number of ethylene oxide repeating units. To better understand the mechanism of different packing frameworks controlled by different inducing ligands, all-atom molecular dynamic (MD) simulations were performed. The MD simulation focused on the dynamic dimerization behavior of ConA-RnM system, which revealed clear relationships between the length of inducing ligands and ConA crystalline. In short, besides protein-packing framework control via different crystallization methods, inducing ligands RnM with suitable spacer lengths (n = 3, 4) also play an important role in desired and stable crystalline frameworks.

中文翻译：

---

蛋白质结晶过程中超分子相互作用与蛋白质-蛋白质相互作用之间的竞争：结晶方法和小分子桥的影响

我们引入了一种小分子“诱导配体”策略，通过双重非共价相互作用使蛋白质结晶。在这里，我们证明了伴刀豆球蛋白A（ConA）与配体结合的变体蛋白质包装框架是由不同的结晶方法控制的。此外，蛋白质的结晶构架也受小分子诱导配体R n M（n = 1-5）的控制，该配体的环氧乙烷重复单元数不同。为了更好地理解由不同诱导配体控制的不同堆积骨架的机理，进行了全原子分子动力学（MD）模拟。MD模拟关注ConA - R n M的动态二聚化行为系统，揭示了诱导配体的长度和ConA晶体之间的明确关系。简而言之，除了通过不同的结晶方法控制蛋白质堆积构架之外，具有合适间隔区长度（n = 3，4）的诱导配体R n M在所需和稳定的结晶构架中也起着重要的作用。