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抑制剂对溴结构域蛋白4的两个溴结构域选择机制的多副本分子动力学模拟和自由能分析
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作者 李梦 刘新国 +3 位作者 张少龙 孙嘉豪 张庆刚 陈建中 《Chinese Journal of Chemical Physics》 SCIE EI CAS CSCD 2023年第6期725-739,I0029-I0035,I0057,共23页
溴结构域蛋白4在细胞周期调节中至关重要,已成为治疗各种癌症的潜在靶标、溴结构域蛋白4包含两个溴结构域,即BD1和BD2.研究表明,选择性地抑制BD1或BD2可能提供更有效的治疗方案.因此,了解抑制剂对BD1和BD2结合的选择性机制对于开发BD1和... 溴结构域蛋白4在细胞周期调节中至关重要,已成为治疗各种癌症的潜在靶标、溴结构域蛋白4包含两个溴结构域,即BD1和BD2.研究表明,选择性地抑制BD1或BD2可能提供更有效的治疗方案.因此,了解抑制剂对BD1和BD2结合的选择性机制对于开发BD1和BD2的高选择性抑制剂至关重要.本文利用多副本分子动力学模拟研究了抑制剂SG3-179、GSK778和GSK620对BD1和BD2的结合选择性.结果显示,BD1比BD2具有更强的结构灵活性,而且BD1和BD2表现出不同的内部动力学.对自由能景观的分析表明,BD1和BD2的构象分布存在明显的差异.结合自由能预测表明,熵变、静电相互作用和范德华相互作用是SG3-179、GSK778和GSK620对BD1和BD2选择性结合的关键因素.单个残基能量贡献的计算表明,(BD1,BD2)中的残基(W81,W374)、(P82,P375)、(Q85,K378)、(V87,V380)、(L92,L385)、(N93,G386)、(L94,L387)、(C136,C429)、(N140,N433)、(K141,P434)、(D144,H437)和(I146,V439)在SG3-179、GSK778和GSK620与BD1和BD2的结合中产生明显的能量差异,它们可以作为开发针对BD1或BD2的高选择性抑制剂的有效靶点.相关信息可为提高抑制剂对BD1和BD2的选择性提供重要的理论指导. 展开更多
关键词 溴结构域 结合选择性 多副本分子动力学模拟 自由能预测
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Stabilizing perovskite nanocrystals by controlling protective surface ligands density 被引量:5
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作者 Weilin Zheng Zhichun Li +5 位作者 Congyang zhang Bo Wang qinggang zhang Qun Wan Long Kong Liang Li 《Nano Research》 SCIE EI CAS CSCD 2019年第6期1461-1465,共5页
After nanocrystals synthesis,the purification process with anti-solvents is an essential step to get clean nanocrystals,which could get rid of the by-products of the synthesis.It is generally recognized that this proc... After nanocrystals synthesis,the purification process with anti-solvents is an essential step to get clean nanocrystals,which could get rid of the by-products of the synthesis.It is generally recognized that this process could bring a positive effect for the afterward optoelectronic applications.Unfortunately,we found that the optical properties and photostability of perovskite CsPbBr3 nanocrystals were unavoidably deteriorated after they were washed with anti-solvents,and this deterioration is strongly related to the decreasing of surface ligands density.Therefore,in this paper,we tried to purposely not wash the CsPbBr3 nanocrystals solution after adding didodecyl dimethylammonium bromide (DDAB),and found the existing of DDAB in solution could result in a dramatically enhanced photostability.Inspired by these results,we proposed a new strategy to stabilize perovskite nanocrystals from the view of packaging process:adding protective ligands into the perovskite nanocrystals resin directly,then encapsulating them on blue light-emitting diodes (LED) chips.Surprisingly,stable LED devices (20 mA,2.7V) were achieved by this way,which can keep 80% of the initial photoluminescence (PL) intensity for more than 50 h,while the devices with CsPbBr3 nanocrystals without adding protective ligands into resin dropped to 50% of their initial PL intensity within 6 h.This approach offers a new thought to stabilize perovskite nanocrystals as down-conversion phosphor in quantum dots liquid crystal display. 展开更多
关键词 PEROVSKITE NANOCRYSTALS purification ligand DENSITY PHOTOSTABILITY ENCAPSULATION strategy
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