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      Analyses of the Binding between Water Soluble C60 Derivatives and Potential Drug Targets through a Molecular Docking Approach

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          Abstract

          Fullerene C60, a unique sphere-shaped molecule consisting of carbon, has been proved to have inhibitory effects on many diseases. However, the applications of C60 in medicine have been severely hindered by its complete insolubility in water and low solubility in almost all organic solvents. In this study, the water-soluble C60 derivatives and the C60 binding protein’s structures were collected from the literature. The selected proteins fall into several groups, including acetylcholinesterase, glutamate racemase, inosine monophosphate dehydrogenase, lumazine synthase, human estrogen receptor alpha, dihydrofolate reductase and N-myristoyltransferase. The C60 derivatives were docked into the binding sites in the proteins. The binding affinities of the C60 derivatives were calculated. The bindings between proteins and their known inhibitors or native ligands were also characterized in the same way. The results show that C60 derivatives form good interactions with the binding sites of different protein targets. In many cases, the binding affinities of C60 derivatives are better than those of known inhibitors and native ligands. This study demonstrates the interaction patterns of C60 derivatives and their binding partners, which will have good impact on the fullerene-based drug discovery.

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          Most cited references63

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          Alzheimer disease in the US population: prevalence estimates using the 2000 census.

          Current and future estimates of Alzheimer disease (AD) are essential for public health planning. To provide prevalence estimates of AD for the US population from 2000 through 2050. Alzheimer disease incidence estimates from a population-based, biracial, urban study, using a stratified random sampling design, were converted to prevalence estimates and applied to US Census Bureau estimates of US population growth. A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill, applied to the US population. Alzheimer disease incidence was measured in 3838 persons free of AD at baseline; 835 persons were evaluated for disease incidence. Main Outcome Measure Current and future estimates of prevalence of clinically diagnosed AD in the US population. In 2000, there were 4.5 million persons with AD in the US population. By 2050, this number will increase by almost 3-fold, to 13.2 million. Owing to the rapid growth of the oldest age groups of the US population, the number who are 85 years and older will more than quadruple to 8.0 million. The number who are 75 to 84 years old will double to 4.8 million, while the number who are 65 to 74 years old will remain fairly constant at 0.3 to 0.5 million. The number of persons with AD in the US population will continue to increase unless new discoveries facilitate prevention of the disease.
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            The generalized Born/volume integral implicit solvent model: estimation of the free energy of hydration using London dispersion instead of atomic surface area.

            A new generalized Born model for estimating the free energy of hydration is presented. The new generalized Born/volume integral (GB/VI) estimates the free energy of hydration as a classical electrostatic energy plus a cavitation energy that is not based upon atomic surface area (SA) used in GB/SA hydration models but on a VI London dispersion energy estimated from quantities already calculated in the classical electrostatic energy. The (relatively few) GB/VI model parameters are fitted to experimental data, and parameterizations for two different atomic partial charge models are presented. Comparison of the calculated and experimental free energies of hydration for 560 small molecules (both neutral and charged) shows good agreement (r(2) = 0.94). (c) 2008 Wiley Periodicals, Inc.
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              Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase.

              Binding sites of Torpedo acetylcholinesterase (EC 3.1.1.7) for quaternary ligands were investigated by x-ray crystallography and photoaffinity labeling. Crystal structures of complexes with ligands were determined at 2.8-A resolution. In a complex with edrophonium, and quaternary nitrogen of the ligand interacts with the indole of Trp-84, and its m-hydroxyl displays bifurcated hydrogen bonding to two members of the catalytic triad, Ser-200 and His-440. In a complex with tacrine, the acridine is stacked against the indole of Trp-84. The bisquaternary ligand decamethonium is oriented along the narrow gorge leading to the active site; one quaternary group is apposed to the indole of Trp-84 and the other to that of Trp-279, near the top of the gorge. The only major conformational difference between the three complexes is in the orientation of the phenyl ring of Phe-330. In the decamethonium complex it lies parallel to the surface of the gorge; in the other two complexes it is positioned to make contact with the bound ligand. This close interaction was confirmed by photoaffinity labelling by the photosensitive probe 3H-labeled p-(N,N-dimethylamino)benzenediazonium fluoroborate, which labeled, predominantly, Phe-330 within the active site. Labeling of Trp-279 was also observed. One mole of label is incorporated per mole of AcChoEase inactivated, indicating that labeling of Trp-279 and that of Phe-330 are mutually exclusive. The structural and chemical data, together, show the important role of aromatic groups as binding sites for quaternary ligands, and they provide complementary evidence assigning Trp-84 and Phe-330 to the "anionic" subsite of the active site and Trp-279 to the "peripheral" anionic site.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 February 2016
                2016
                : 11
                : 2
                : e0147761
                Affiliations
                [1 ]Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, China
                [2 ]Key Laboratory of Molecular Biophysics, Ministry of Education, Wuhan, Hubei, China
                [3 ]Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, China
                Wake Forest University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist

                Conceived and designed the experiments: HZ MJ. Performed the experiments: MJ. Analyzed the data: MJ HZ. Contributed reagents/materials/analysis tools: JL EAA. Wrote the paper: HZ MJ.

                Article
                PONE-D-15-26448
                10.1371/journal.pone.0147761
                4735121
                26829126
                d1aad7eb-8204-4923-b343-0eaadb65db2b
                © 2016 Junaid et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 June 2015
                : 7 January 2016
                Page count
                Figures: 9, Tables: 0, Pages: 21
                Funding
                This work is financially supported by National Key Basic Research Program of China (No. 2013CB933900).
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Physical Chemistry
                Chemical Bonding
                Hydrogen Bonding
                Biology and Life Sciences
                Biochemistry
                Neurochemistry
                Neurotransmitters
                Glutamate
                Biology and Life Sciences
                Neuroscience
                Neurochemistry
                Neurotransmitters
                Glutamate
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzymes
                Proteases
                Serine Proteases
                Biology and Life Sciences
                Biochemistry
                Proteins
                Enzymes
                Proteases
                Serine Proteases
                Biology and Life Sciences
                Biochemistry
                Hormones
                Estrogens
                Medicine and Health Sciences
                Pharmacology
                Drug Interactions
                Medicine and Health Sciences
                Pharmacology
                Drug Research and Development
                Drug Discovery
                Physical Sciences
                Physics
                Condensed Matter Physics
                Solid State Physics
                Crystallography
                Crystal Structure
                Biology and Life Sciences
                Biochemistry
                Glycobiology
                Glycosylamines
                Nucleosides
                Inosine
                Custom metadata
                All relevant data are within the paper and its Supporting Information file.

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                Uncategorized

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