Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 77900 Olomouc, Czech Republic.
J Chem Inf Model. 2020 Dec 28;60(12):6074-6080. doi: 10.1021/acs.jcim.0c00792. Epub 2020 Nov 9.
Synthetic feasibility of compounds generated with de novo approaches is one of the main issues, which may limit their applicability. Many of the de novo generation approaches do not address this issue. Here, we studied the recently implemented chemically reasonable mutations approach (CReM) and the ways how one could indirectly control synthetic complexity of generated compounds and how this affected the target scores for Guacamol benchmark tasks. We found a clear trade-off between synthetic complexity and target scores and demonstrated that CReM-based solutions were competitive to reference approaches, which were explicitly biased by synthetic feasibility of generated compounds.
从头开始生成的化合物的合成可行性是主要问题之一，这可能限制它们的适用性。许多从头开始的生成方法都没有解决这个问题。在这里，我们研究了最近实施的化学合理突变方法（CReM），以及如何间接控制生成化合物的合成复杂性，以及这如何影响 Guacamol 基准任务的目标分数。我们发现合成复杂性和目标分数之间存在明显的权衡，并且证明了基于 CReM 的解决方案与参考方法具有竞争力，参考方法明确偏向于生成化合物的合成可行性。
