通过3D-SMINBR发现制药性共晶:一种通过3D分子构造增强的新型网络推工具
Lulu Zheng1, Bin Zhu2, Zengrui Wu1
1Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Laboratory of Molecular Modeling & Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Journal of chemical information and modeling
|July 3, 2023
概括
一个新的计算工具,3D-SMINBR,通过整合3D分子数据和网络分析,有助于发现药用共晶体. 这种方法提高了辅助器的预测,增强了药物特性,如溶解度.
科学领域:
- * 制药科学 制药科学
- * 计算化学 计算机化学
- * 材料科学 材料科学
背景情况:
- * 晶具有改善药物的物理化学和生物制药性能的巨大潜力.
- * 确定适合于药物共晶形成的共构体仍然是一个挑战.
- *现有的计算方法可能无法完全捕捉共晶相互作用的复杂性.
研究的目的:
- * 开发和验证一种新的*in silico*工具,即基于3D亚结构-分子相互作用网络的建议 (3D-SMINBR),用于预测药物共晶共构体.
- *通过将3D分子构造与基于网络的推模型相结合,增强共晶的发现.
- *为了证明3D-SMINBR在识别具有改进性质的有前途的共晶的实际实用性.
主要方法:
- * 3D分子形状与基于权重网络的推模型的整合.
- * 开发3D-SMINBR计算工具,以优先考虑潜在的协同构造者.
- *与基于二维子结构的模型 (SMINBR) 进行交叉验证,并对未见的共晶数据进行测试.
- * 案例研究涉及对阿米拉里辛A和异 Imperatorin 的共晶查.
主要成果:
- * 3D-SMINBR在交叉验证中表现出与之前的基于2D的SMINBR模型相比更好的性能.
- * 该工具在新型的共晶数据集上表现出强大的概括能力.
- *案例研究成功地确定了具有增强溶解性和溶解率的共晶体 (Arm-piperazine,iIM-salicylamide).
- * 开发的共晶体比其母药物表现得更好.
结论:
- *3D-SMINBR,通过3D分子构造增强,是一种有效的基于网络的工具,用于加速共晶发现.
- * *in silico*方法显著有助于识别合适的共同形成物,克服了共同晶体发育中的一个关键障碍.
- * 该工具的实际应用和验证的性能表明其在药物研发中的价值.
- *为3D-SMINBR提供免费的Web服务器,以便在科学界更广泛地访问和使用.
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