Host–guest binding remains a major challenge in modern computational modelling. The newest 7th statistical assessment of the modeling of proteins and ligands (SAMPL) challenge contains a new series of host–guest systems. The TrimerTrip host binds to 16 structurally diverse guests. Previously, we have successfully employed the spherical coordinates as the collective variables coupled with the enhanced sampling technique metadynamics to enhance the sampling of the binding/unbinding event, search for possible binding poses and calculate the binding affinities in all three host–guest binding cases of the 6th SAMPL challenge. In this work, we report a retrospective study on the TrimerTrip host–guest systems by employing the same protocol to investigate the TrimerTrip host in the SAMPL7 challenge. As no binding pose is provided by the SAMPL7 host, our simulations initiate from randomly selected configurations and are proceeded long enough to obtain converged free energy estimates and search for possible binding poses. The calculated binding affinities are in good agreement with the experimental reference, and the obtained binding poses serve as a nice starting point for end-point or alchemical free energy calculations. Note that as the work is performed after the close of the SAMPL7 challenge, we do not participate in the challenge and the results are not formally submitted to the SAMPL7 challenge.

主客绑定仍然是现代计算建模中的主要挑战。蛋白质和配体建模 (SAMPL) 挑战的最新第 7 次统计评估包含一系列新的主客体系统。TrimerTrip 宿主与 16 个结构不同的客人结合。以前，我们已经成功地采用球坐标作为集体变量，结合增强的采样技术元动力学来增强结合/解绑事件的采样，搜索可能的结合姿势并计算所有三种宿主 - 客体结合情况下的结合亲和力。第 6 次 SAMPL 挑战。在这项工作中，我们通过使用相同的协议来调查 SAMPL7 挑战中的 TrimerTrip 主机，报告了对 TrimerTrip 主机-访客系统的回顾性研究。由于 SAMPL7 主机不提供绑定姿势，我们的模拟从随机选择的配置开始，并进行足够长的时间以获得收敛的自由能估计并搜索可能的结合姿势。计算出的结合亲和力与实验参考非常吻合，获得的结合姿势可作为终点或炼金术自由能计算的良好起点。请注意，由于工作是在 SAMPL7 挑战赛结束后进行的，我们不参与挑战赛，结果也不会正式提交给 SAMPL7 挑战赛。并且获得的结合姿势可以作为终点或炼金术自由能计算的一个很好的起点。请注意，由于工作是在 SAMPL7 挑战赛结束后进行的，我们不参与挑战赛，结果也不会正式提交给 SAMPL7 挑战赛。并且获得的结合姿势可以作为终点或炼金术自由能计算的一个很好的起点。请注意，由于工作是在 SAMPL7 挑战赛结束后进行的，我们不参与挑战赛，结果也不会正式提交给 SAMPL7 挑战赛。