Virtual Coformer Screening by Crystal Structure Predictions: Crucial Role of Crystallinity in Pharmaceutical Cocrystallization.
Virtual Coformer Screening by Crystal Structure Predictions: Crucial Role of Crystallinity in Pharmaceutical Cocrystallization.
复制标题
通过晶体结构预测进行虚拟共形成体筛选：结晶度在药物共结晶中的关键作用。
DOI：
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复制
发表时间：
2020
影响因子：
5.7
通讯作者：
Y. Abramov
中科院分区：
文献类型：
--
作者：
Guangxu Sun;Yingdi Jin;Sizhu Li;Zhuocen Yang;Baimei Shi;Chao Chang;Y. Abramov
One of the most popular strategies of optimization of drug properties in pharmaceutical industry appears to be a solid form change into a cocrystalline. A number of virtual screening approaches have been previously developed to allow a selection of the most promising cocrystal formers (coformers) for an experimental follow-up. A significant drawback of those methods is related to the lack of accounting for the crystallinity contribution to cocrystal formation. To address this issue, we propose in this study two virtual coformer screening approaches based on a modern cloud-computing crystal structure prediction (CSP) technology at a dispersion-corrected density functional theory (DFT-D) level. The CSP-based methods were for the first time validated on challenging cases of indomethacin and paracetamol cocrystallization, in respect of which the previously developed approaches provided poor predictions. The calculations demonstrated a dramatic improvement of the virtual coformer screening performance relative to the other methods. It is demonstrated that the crystallinity contribution to the formation of paracetamol and indomethacin cocrystals is a dominant one, and therefore should not be ignored in the virtual screening calculations. Our results encourage a broad utilization of the proposed CSP-based technology in pharmaceutical industry, as the only virtual coformer screening method, which directly accounts for the crystallinity contribution.
共晶以促进5杆超过5的可溶性化合物的递送。
影响因子：
16.1
作者：
Kuminek G;Cao F;Bahia de Oliveira da Rocha A;Gonçalves Cardoso S;Rodríguez-Hornedo N
通讯作者：
Rodríguez-Hornedo N