论文标题

通过主动设计空间修剪的自我关注的虚拟筛选

Self-focusing virtual screening with active design space pruning

论文作者

Graff, David E., Aldeghi, Matteo, Morrone, Joseph A., Jordan, Kirk E., Pyzer-Knapp, Edward O., Coley, Connor W.

论文摘要

高通量虚拟筛选是在发现小分子中使用的必不可少的技术。如果分子库非常大,那么详尽的虚拟屏幕的成本可能会令人望而却步。与随机选择相比,模型指导的优化通过样本效率的急剧提高来降低这些成本。但是,这些技术通过替代模型培训和推理步骤为工作流带来了新的成本。在这项研究中,我们提出了模型引导优化框架的扩展,该框架使用我们称为设计空间修剪(DSP)的技术来降低推论成本,该技术不可逆地从考虑中删除了表现不佳的候选人。我们研究了DSP在各种优化任务中的应用,并观察到间接成本的显着降低,同时表现出与基线优化相似的性能。 DSP代表了模型引导优化的有吸引力的扩展,该扩展可能会限制优化设置中的间接费用,这些优化设置相对于客观成本(例如对接),这些成本不可忽略不计。

High-throughput virtual screening is an indispensable technique utilized in the discovery of small molecules. In cases where the library of molecules is exceedingly large, the cost of an exhaustive virtual screen may be prohibitive. Model-guided optimization has been employed to lower these costs through dramatic increases in sample efficiency compared to random selection. However, these techniques introduce new costs to the workflow through the surrogate model training and inference steps. In this study, we propose an extension to the framework of model-guided optimization that mitigates inferences costs using a technique we refer to as design space pruning (DSP), which irreversibly removes poor-performing candidates from consideration. We study the application of DSP to a variety of optimization tasks and observe significant reductions in overhead costs while exhibiting similar performance to the baseline optimization. DSP represents an attractive extension of model-guided optimization that can limit overhead costs in optimization settings where these costs are non-negligible relative to objective costs, such as docking.

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