Pandey Ankit, Costa Gustavo J, Alam Mushfiq, Poirier Bill, Liang Ruibin
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States.
J Chem Theory Comput. 2025 May 13;21(9):4704-4717. doi: 10.1021/acs.jctc.5c00324. Epub 2025 May 1.
The parallel on-the-fly algorithm is a new, efficient global search algorithm for exploring single-state potential energy surfaces and conical intersection seam spaces of a wide range of molecules. Despite major developments, its application to complex molecular systems, especially in the condensed phase, remains challenging due to the high dimensionality of the configurational space. In this work, we address this challenge and extend its applicability to the reaction discovery of large and complex molecular photoswitches in various molecular environments, including in the condensed phase with explicit solvent molecules. This is achieved by performing an explicit exploration of a comparatively large configurational subspace, while gradually relaxing the remaining degrees of freedom. The new algorithm is applied to the reaction discovery of bilirubin and donor-acceptor Stenhouse adducts, a next-generation class of molecular photoswitches, in vacuum and in the aqueous solution. To this end, we designed an automated and systematic workflow for to discover and characterize new minima and low-energy reaction pathways in these challenging and complex systems. Our findings demonstrate the algorithm's effectiveness in quickly exploring the configuration space and uncovering kinetically accessible products, offering new insights into the intricate chemical reactivities of these molecules and the roles of molecular environments on the reaction pathways. The results underscore the promising potential of parallelized global exploration methods for reaction discovery in biomolecular systems.
并行实时算法是一种新型高效的全局搜索算法，用于探索各种分子的单态势能面和锥形交叉缝空间。尽管取得了重大进展，但由于构型空间的高维性，将其应用于复杂分子系统，尤其是凝聚相中的分子系统，仍然具有挑战性。在这项工作中，我们应对了这一挑战，并将其适用性扩展到各种分子环境中大型复杂分子光开关的反应发现，包括含有明确溶剂分子的凝聚相。这是通过对一个相对较大的构型子空间进行显式探索，同时逐步放松其余自由度来实现的。新算法应用于胆红素和供体-受体斯滕豪斯加合物（一类下一代分子光开关）在真空和水溶液中的反应发现。为此，我们设计了一个自动化且系统的工作流程，以在这些具有挑战性的复杂系统中发现并表征新的极小值和低能反应路径。我们的研究结果证明了该算法在快速探索构型空间和揭示动力学上可及产物方面的有效性，为这些分子复杂的化学反应性以及分子环境在反应路径中的作用提供了新的见解。结果强调了并行全局探索方法在生物分子系统反应发现中的广阔前景。
