Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, le...Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.展开更多
A new process for extracting indium from indium-zinc concentrates was proposed.The process can directly extract indium from removed copper solution by D2EHPA,and cancel the stage of removing iron in the traditional pr...A new process for extracting indium from indium-zinc concentrates was proposed.The process can directly extract indium from removed copper solution by D2EHPA,and cancel the stage of removing iron in the traditional process because of using iron and part of zinc in the In-Zn concentrates for direct preparing high quality Mn-Zn soft magnetic ferrites.The technologies in the processes,such as leaching the neutral leached residues with high concentrated acid at high temperature,reduction ferric and removing copper,and extracting indium,were investigated.The results show that total recovery ratio of indium is increased from less than 70% in the traditional process to more than 95%.This process has the advantages of largely simplifying the procedure of indium extraction,zero draining off of iron residue and zero emitting of SO2.So this is a clean production process.展开更多
基金supported by National Key R&D Program of China (No.2016YFA0501700)National Natural Science Foundation of China (No.21433004, No.31700646, No.91753103)+1 种基金Innovation Program of Shanghai Municipal Education Commission (201701070005E00020)NYU Global Seed Grant
文摘Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed.
基金Project(2004AA649080) supported by the National Basic Research and Development Program of ChinaProjects(50234010,50444020) supported by the National Natural Science Foundation of China
文摘A new process for extracting indium from indium-zinc concentrates was proposed.The process can directly extract indium from removed copper solution by D2EHPA,and cancel the stage of removing iron in the traditional process because of using iron and part of zinc in the In-Zn concentrates for direct preparing high quality Mn-Zn soft magnetic ferrites.The technologies in the processes,such as leaching the neutral leached residues with high concentrated acid at high temperature,reduction ferric and removing copper,and extracting indium,were investigated.The results show that total recovery ratio of indium is increased from less than 70% in the traditional process to more than 95%.This process has the advantages of largely simplifying the procedure of indium extraction,zero draining off of iron residue and zero emitting of SO2.So this is a clean production process.
