BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug des...BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.展开更多
Aqueous zinc-ion batteries are a kind of attractive power supply devices due to their high energy, environmental benignity, and intrinsic safety. In recent years, tremendous enthusiasm has been devoted to the function...Aqueous zinc-ion batteries are a kind of attractive power supply devices due to their high energy, environmental benignity, and intrinsic safety. In recent years, tremendous enthusiasm has been devoted to the functionalities of aqueous zinc-ion batteries, aiming to extend their potential applications in multiple dimensions and multiple scales. Here, the latest advances in the design, construction, and performance evaluation of aqueous zinc-ion batteries are summarized. The focus is on various functionalities such as flexibility, self-healing, self-charging, and miniaturization. We also highlight the materials and structures that have been engineered to realize these functionalities. Finally, we offer some general insights into the challenges and chances in such exciting field.展开更多
我国北方地区高渗透率风电场和高比例热电联产（combined heat and power,CHP）机组的电源结构给电力系统调度和运行控制带来了巨大挑战。通过CHP机组与集中供热系统协调配合,释放CHP机组灵活性潜力是解决这一问题的有效手段。但是,CHP...我国北方地区高渗透率风电场和高比例热电联产（combined heat and power,CHP）机组的电源结构给电力系统调度和运行控制带来了巨大挑战。通过CHP机组与集中供热系统协调配合,释放CHP机组灵活性潜力是解决这一问题的有效手段。但是,CHP机组灵活性有限且难以度量,如何利用CHP机组的灵活性来协调满足电力系统调度和运行控制的不同需求,是高效、安全发挥CHP机组灵活性的前提。基于此,该文从电力系统调度和控制时间尺度角度定义了CHP机组多时间尺度灵活性,提出了满足CHP机组多时间尺度灵活性释放的CHP机组与热网系统协调模型。建立了电热系统联合调度框架：集中供热系统给出满足最大化CHP机组电出力灵活性的CHP机组允许热出力区间,电力系统以允许热出力区间为电热系统运行边界,实现CHP机组多时间尺度灵活性的最优分配。采用电/热联合系统算例,研究了高渗透率风电条件下CHP机组多时间尺度灵活性对风电消纳以及系统备用需求的影响,算例结果验证了该文所提方法的有效性和优越性。展开更多
基金supported by the National Natural Science Foundation of China(21102181,81302634 and 21572273)
文摘BRAF has been recognized as a promising target for cancer therapy. A number of crystal structures have been published. Molecular docking is one of the most effective techniques in the field of computer-aided drug design（CADD）. Appropriate protein conformation and docking method are essential for the successful virtual screening experiments. One approach considering protein flexibility and multiple docking methods was proposed in this study. Six DFG-in/αC-helix-out crystal structures of BRAF, three docking programs（Glide, GOLD and Ligand Fit） and 12 scoring functions were applied for the best combination by judging from the results of pose prediction and retrospective virtual screening（VS）. The most accurate results（mean RMSD of about 0.6 A） of pose prediction were obtained with two complex structures（PDB： 3 C4 C and 3 SKC） using Glide SP. From the retrospective VS, the most active compounds were identified by using the complex structure of 3 SKC, indicated by a ROC/AUC score of 0.998 and an EF of 20.6 at 5% of the database screen with Glide-SP. On the whole, PDB 3 SKC could achieve a higher rate of correct reproduction, a better enrichment and more diverse compounds. A comparison of 3 SKC and the other X-ray crystal structures led to a rationale for the docking results. PDB 3 SKC could achieve a broad range of sulfonamide substitutions through an expanded hydrophobic pocket formed by a further shift of the αC-helix. Our study emphasized the necessity and significance of protein flexibility and scoring functions in both ligand docking and virtual screening.
基金Sponsored by the Fundamental Research Program of Shanxi Province (Grant No.202103021223019)the Science and Technology Major Project of Shanxi (Grant No. 202101030201022)+1 种基金the National Natural Science Foundation of China (Grant Nos.52172219, 51872192)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No.19KJA170001)。
文摘Aqueous zinc-ion batteries are a kind of attractive power supply devices due to their high energy, environmental benignity, and intrinsic safety. In recent years, tremendous enthusiasm has been devoted to the functionalities of aqueous zinc-ion batteries, aiming to extend their potential applications in multiple dimensions and multiple scales. Here, the latest advances in the design, construction, and performance evaluation of aqueous zinc-ion batteries are summarized. The focus is on various functionalities such as flexibility, self-healing, self-charging, and miniaturization. We also highlight the materials and structures that have been engineered to realize these functionalities. Finally, we offer some general insights into the challenges and chances in such exciting field.
文摘我国北方地区高渗透率风电场和高比例热电联产（combined heat and power,CHP）机组的电源结构给电力系统调度和运行控制带来了巨大挑战。通过CHP机组与集中供热系统协调配合,释放CHP机组灵活性潜力是解决这一问题的有效手段。但是,CHP机组灵活性有限且难以度量,如何利用CHP机组的灵活性来协调满足电力系统调度和运行控制的不同需求,是高效、安全发挥CHP机组灵活性的前提。基于此,该文从电力系统调度和控制时间尺度角度定义了CHP机组多时间尺度灵活性,提出了满足CHP机组多时间尺度灵活性释放的CHP机组与热网系统协调模型。建立了电热系统联合调度框架：集中供热系统给出满足最大化CHP机组电出力灵活性的CHP机组允许热出力区间,电力系统以允许热出力区间为电热系统运行边界,实现CHP机组多时间尺度灵活性的最优分配。采用电/热联合系统算例,研究了高渗透率风电条件下CHP机组多时间尺度灵活性对风电消纳以及系统备用需求的影响,算例结果验证了该文所提方法的有效性和优越性。
