In recent years, free energy perturbation calculations have garnered increasing attention as tools to support drug discovery. The lead optimization mapper (Lomap) was proposed as an algorithm to calculate the relative free energy between ligands efficiently. However, Lomap requires checking whether each edge in the FEP graph is removable, which necessitates checking the constraints for all edges. Consequently, conventional Lomap requires significant computation time, at least several hours for cases involving hundreds of compounds, and is impractical for cases with more than tens of thousands of edges. In this study, we aimed to reduce the computational cost of Lomap to enable the construction of FEP graphs for hundreds of compounds. We can reduce the overall number of constraint checks required from an amount dependent on the number of edges to one dependent on the number of nodes by using the chunk check process to check the constraints for as many edges as possible simultaneously. Based on the analysis of the execution profiles, we also improved the speed of cycle constraint and diameter constraint checks. Moreover, the output graph is the same as that obtained using the conventional Lomap, enabling direct replacement of the original one with our method. With our improvement, the execution was hundreds of times faster than that of the original Lomap.

近年来，自由能微扰计算作为支持药物发现的工具受到越来越多的关注。先导优化映射器（Lomap）被提出作为一种有效计算配体之间相对自由能的算法。然而，Lomap需要检查FEP图中的每条边是否可移除，这就需要检查所有边的约束。因此，传统的 Lomap 需要大量的计算时间，对于涉及数百种化合物的情况至少需要几个小时，并且对于具有超过数万条边的情况是不切实际的。在本研究中，我们的目标是降低 Lomap 的计算成本，以便能够构建数百种化合物的 FEP 图。通过使用块检查过程同时检查尽可能多的边的约束，我们可以将所需的约束检查总数从依赖于边数的数量减少到依赖于节点数的数量。基于执行配置文件的分析，我们还提高了循环约束和直径约束检查的速度。此外，输出图与使用传统 Lomap 获得的图相同，可以用我们的方法直接替换原始图。经过我们的改进，执行速度比原来的 Lomap 快了数百倍。