The microscopic mechanisms of ion hydration and ion selectivity in biomolecular systems are long-standing research topics, in which the difficulty is how to reasonably and accurately describe the ion-water and ion-bio...The microscopic mechanisms of ion hydration and ion selectivity in biomolecular systems are long-standing research topics, in which the difficulty is how to reasonably and accurately describe the ion-water and ion-biomolecule interactions. This paper summarizes the development and applications of the atom-bond electronegativity equalization fluctuating charge force field model, ABEEM/MM, in the investigations of ion hydration, metalloproteins and ion-DNA bases systems. Based on high-level quantum chemistry calculations, the parameters were optimized and the molecular potential functions were constructed and applied to studies of structures, activities, energetics, and thermodynamic and kinetic properties of these ion-containing sys- tems. The results show that the performance of ABEEM]MM is generally better than that of the common force fields, and its accuracy can reach or approach that of the hlgh-level ab initio MP2 method. These studies provide a solid basis for further investigations of ion selectivity in biomolecular systems, the structures and properties of metalloproteins and other related ion-containing systems.展开更多
Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and fu...Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and functions.Myoglobin(Mb),a small heme protein created by nature with diverse functions,has been shown to be an ideal scaffold for rational protein design.The progress reviewed herein includes fine-tuning its native functions of O2binding and transport,peroxidase activity and nitrite reductase(NIR)activity,and rational expanding its functionalities to peroxygenase,heme-copper oxidase(HCO),nitric oxide reductase(NOR),as well as hydroxylamine reductase.These studies have enhanced our understanding of how metalloproteins work in nature,and provided insights for rational design of functional metalloproteins for practical applications in the future.展开更多
In the construction of biosensors, enzymes function as mediators converting biological signals generated by specific biological processes, into electrochemical signals. The ideology of bio-sensor design is retention o...In the construction of biosensors, enzymes function as mediators converting biological signals generated by specific biological processes, into electrochemical signals. The ideology of bio-sensor design is retention of electron transfer activity of the enzyme utilizing superior interfacial architecture. In this work a Schiff-base macromolecule has been synthesized by reflux of 2, 3-diaminonaphthalene and pyrrole-2-carboxaldehyde starting materials. The Schiff-base ligand was subsequently complexed with FeCl2?4H2O under reflux, to produce the Fe-Schiff-base complex. The Schiff-base ligand and Fe-Schiff-base complex were characterized using nuclear magnetic resonance (NMR) spectroscopy, Ultra Violet/Visible (UV/Vis) spectroscopy, Fourier transfer infrared resonance (FTIR) and electron energy loss spectroscopy (EELS) to confirm the structure of the synthesis products. NMR spectroscopy confirmed the imide linkage of Schiff-base formation as two symmetrical peaks at 8.1 and 7.7 ppm respectively. Comparison of starting materials and product spectra by UV/Vis spectroscopy confirmed the disappearance of the diaminonaphthalene peak at 250 nm as evidence of complete conversion to product. FTIR spectroscopy of the Schiff-base ligand confirmed the formation of the imine bond at 1595 cm-1. EELS spectra comparing FeCl2?4H2O and the Fe-Schiff-base complex, showed good agreement in the energy loss profiles associated with changes to the electronic arrangement of Fe d-orbitals. EDS clearly identified a spectral band for Fe (7 - 8 eV) in the Fe-Schiff-base complex. Electrochemical evaluation of the Fe-Schiff-base complex was compared to the electrochemical signature of denatured cytochrome-C using cyclic voltammetry and square wave voltammetry. The Fe2+/Fe3+ quasi-reversible behavior for iron in the metallated complex was observed at -0.430 V vs. Ag/AgCl, which is consistent with reference values for iron in macromolecular structures.展开更多
Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metallop...Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metalloproteins.In this study,the AutoDock package was employed to example docking into a di-iron binding protein,bacterioferritin.Each binding site of this protein was tested for docking with iron ions.Blind docking experiments showed that all docking conformations converged into two clusters,one for internal iron binding in sites within the metalloprotein and the other for external iron binding on the protein surface.Local docking experiments showed that there were significant differences between two internal iron binding sites.Docking at one site gave a reasonable root-mean-square deviation(RMSD) distribution with relatively low binding energy.Analysis of the binding mode quality for this site revealed that more than half of the docking conformations were categorized as having good binding geometry,while no good conformations were found for the other site.Further investigations indicated that coordinating water molecules contributed to the stability of binding geometries.This study provides an empirical approach towards the study of molecular docking in metalloproteins.展开更多
基金supported by the National Natural Science Foundation of China(21133005 and 20703022)
文摘The microscopic mechanisms of ion hydration and ion selectivity in biomolecular systems are long-standing research topics, in which the difficulty is how to reasonably and accurately describe the ion-water and ion-biomolecule interactions. This paper summarizes the development and applications of the atom-bond electronegativity equalization fluctuating charge force field model, ABEEM/MM, in the investigations of ion hydration, metalloproteins and ion-DNA bases systems. Based on high-level quantum chemistry calculations, the parameters were optimized and the molecular potential functions were constructed and applied to studies of structures, activities, energetics, and thermodynamic and kinetic properties of these ion-containing sys- tems. The results show that the performance of ABEEM]MM is generally better than that of the common force fields, and its accuracy can reach or approach that of the hlgh-level ab initio MP2 method. These studies provide a solid basis for further investigations of ion selectivity in biomolecular systems, the structures and properties of metalloproteins and other related ion-containing systems.
基金supported by the National Natural Science Foundation of China(21101091,31370812)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China.J.Wang is supported by the National Basic Research Program of China(2010CB912301,2009CB82 5505)+1 种基金the National Natural Science Foundation of China(90913022)Y.Lu is supported by the US National Institute of Health(GM062211)
文摘Rational protein design is a powerful strategy,not only for revealing the structure and function relationship of natural metalloproteins,but also for creating artificial metalloproteins with improved properties and functions.Myoglobin(Mb),a small heme protein created by nature with diverse functions,has been shown to be an ideal scaffold for rational protein design.The progress reviewed herein includes fine-tuning its native functions of O2binding and transport,peroxidase activity and nitrite reductase(NIR)activity,and rational expanding its functionalities to peroxygenase,heme-copper oxidase(HCO),nitric oxide reductase(NOR),as well as hydroxylamine reductase.These studies have enhanced our understanding of how metalloproteins work in nature,and provided insights for rational design of functional metalloproteins for practical applications in the future.
文摘In the construction of biosensors, enzymes function as mediators converting biological signals generated by specific biological processes, into electrochemical signals. The ideology of bio-sensor design is retention of electron transfer activity of the enzyme utilizing superior interfacial architecture. In this work a Schiff-base macromolecule has been synthesized by reflux of 2, 3-diaminonaphthalene and pyrrole-2-carboxaldehyde starting materials. The Schiff-base ligand was subsequently complexed with FeCl2?4H2O under reflux, to produce the Fe-Schiff-base complex. The Schiff-base ligand and Fe-Schiff-base complex were characterized using nuclear magnetic resonance (NMR) spectroscopy, Ultra Violet/Visible (UV/Vis) spectroscopy, Fourier transfer infrared resonance (FTIR) and electron energy loss spectroscopy (EELS) to confirm the structure of the synthesis products. NMR spectroscopy confirmed the imide linkage of Schiff-base formation as two symmetrical peaks at 8.1 and 7.7 ppm respectively. Comparison of starting materials and product spectra by UV/Vis spectroscopy confirmed the disappearance of the diaminonaphthalene peak at 250 nm as evidence of complete conversion to product. FTIR spectroscopy of the Schiff-base ligand confirmed the formation of the imine bond at 1595 cm-1. EELS spectra comparing FeCl2?4H2O and the Fe-Schiff-base complex, showed good agreement in the energy loss profiles associated with changes to the electronic arrangement of Fe d-orbitals. EDS clearly identified a spectral band for Fe (7 - 8 eV) in the Fe-Schiff-base complex. Electrochemical evaluation of the Fe-Schiff-base complex was compared to the electrochemical signature of denatured cytochrome-C using cyclic voltammetry and square wave voltammetry. The Fe2+/Fe3+ quasi-reversible behavior for iron in the metallated complex was observed at -0.430 V vs. Ag/AgCl, which is consistent with reference values for iron in macromolecular structures.
基金Project (No. 2011-II-010) supported by the Fundamental Research Funds for the Central Universities,China
文摘Various molecular docking software packages are available for modeling interactions between small molecules and proteins.However,there have been few reports of modeling the interactions between metal ions and metalloproteins.In this study,the AutoDock package was employed to example docking into a di-iron binding protein,bacterioferritin.Each binding site of this protein was tested for docking with iron ions.Blind docking experiments showed that all docking conformations converged into two clusters,one for internal iron binding in sites within the metalloprotein and the other for external iron binding on the protein surface.Local docking experiments showed that there were significant differences between two internal iron binding sites.Docking at one site gave a reasonable root-mean-square deviation(RMSD) distribution with relatively low binding energy.Analysis of the binding mode quality for this site revealed that more than half of the docking conformations were categorized as having good binding geometry,while no good conformations were found for the other site.Further investigations indicated that coordinating water molecules contributed to the stability of binding geometries.This study provides an empirical approach towards the study of molecular docking in metalloproteins.
