Wang Xiaohui, Huai Zhe, Sun Zhaoxi
Beijing Leto Laboratories Co., Ltd., Beijing 100083, China.
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Molecules. 2023 Aug 8;28(16):5940. doi: 10.3390/molecules28165940.
Macrocyclic hosts as prototypical receptors to gaseous and drug-like guests are crucial components in pharmaceutical research. The external guests are often coordinated at the center of these macromolecular containers. The formation of host-guest coordination is accompanied by the broken of host-water and host-ion interactions and sometimes also involves some conformational rearrangements of the host. A balanced description of various components of interacting terms is indispensable. However, up to now, the modeling community still lacks a general yet detailed understanding of commonly employed general-purpose force fields and the host dynamics produced by these popular selections. To fill this critical gap, in this paper, we profile the energetics and dynamics of four types of popular macrocycles, including cucurbiturils, pillararenes, cyclodextrins, and octa acids. The presented investigations of force field definitions, refitting, and evaluations are unprecedently detailed. Based on the valuable observations and insightful explanations, we finally summarize some general guidelines on force field parametrization and selection in host-guest modeling.
作为气态和类药物客体的典型受体，大环主体是药物研究中的关键组成部分。外部客体通常在这些大分子容器的中心配位。主客体配位的形成伴随着主体 - 水和主体 - 离子相互作用的破坏，有时还涉及主体的一些构象重排。对相互作用项的各种组成部分进行平衡描述是必不可少的。然而，到目前为止，建模界仍然缺乏对常用通用力场以及这些流行选择所产生的主体动力学的全面而详细的理解。为了填补这一关键空白，在本文中，我们剖析了四种类型的流行大环化合物的能量学和动力学，包括葫芦脲、柱芳烃、环糊精和八元酸。所呈现的对力场定义、重新拟合和评估的研究前所未有的详细。基于这些有价值的观察和深刻的解释，我们最终总结了一些关于主客体建模中力场参数化和选择的一般指导原则。
