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  • 1
    ISSN: 0948-5023
    Keywords: HIV-1 reverse transcriptase ; Minor groove binding track ; Particle-mesh Ewald
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract We have built a molecular dynamics model for human immunodeficiency virus (HIV-1) reverse transcriptase (RT) complexed with a 19/18-mer template/primer by combining the structural information of a low resolution crystal structure of a HIV-1 RT/DNA complex (1hmi) with that of a high resolution crystal structure of unliganded HIV-1 RT (1rtj). The process involved slow forcing of the α-carbons of 1rtj onto those of 1hmi using constrained MD simulations, while immersing the protein in aqueous solution. A similar technique was used to build the bent all-atom DNA duplex, which was then docked into the modeled protein. The resulting model complex was refined using molecular dynamics simulation with the Particle-mesh Ewald method employed to accommodate long-range electrostatic interactions. New parameters of the Amber force field that affect DNA twist are tested and largely validated. The model has been used successfully to explain the results of vertical scanning mutagenesis of residue 266 (Trp266). Recently, the low resolution crystal structure of the HIV-1 RT/DNA complex has been refined to a 2.8 Å resolution (2hmi) and a crystal structure of a HIV-1/RT/dTTP ternary complex has been determined at 3.2 Å resolution (1rtd). A detailed structural comparison of the prior model structure and the two experimental structures becomes possible. Overall, the three structures share many similarities. The root mean square deviations of the α-carbons for the individual subdomains among the three structures are within the same ranges. The secondary structure assignments in the three structures are nearly identical. Key protein-DNA contacts such as those in the region of the primer grip are also similar in the three structures.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0878
    Keywords: Encephalic photoreceptors ; Hypothalamus ; Photoperiodism ; Birds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary In bilaterally enucleated White-crowned Sparrows, Zonotrichia leucophrys gambelii, testicular growth and development at rates similar to those of intact birds subjected to long days, can be induced by illumination of sites within and near the ventromedial hypothalamus from the tips of single, chronically implanted, light-conducting fibers. Essentially identical results are obtained with the same mode of encephalic illumination of birds with intact eyes held on short days that are otherwise nonstimulatory. Examination of the distribution of the sites of the fibers from which weak illumination induced testicular growth, increase in plasma level of luteinizing hormone or increase in plasma level of testosterone suggests that most of the photoreceptors must lie either within the ventromedial hypothalamus or in sites ventral thereto, such as the tuberal complex. For the time being, at least, we find it necessary to assume that some photosensitive elements of the system occur outside of the ventral hypothalamus. We are most grateful to several colleagues at the University of Washington for their generous assistance. Dr. R.B. Pinter, Department of Electrical Engineering and Zoology; Dr. M.M. Harnois, Department of Physics, and Dr. R.J. Spiger, Geophysics Program, made suggestions and rendered invaluable assistance with various aspects of the optical measurements. Dr. John C. Wingfield and Mr. Philip W. Mattocks kindly assayed the plasma samples for luteinizing hormone and androgens. We wish to express our most sincere thanks to Dr. H.-G. Hartwig, Giessen, for his advice and to Miss I. Lyncker, Giessen, for her conscientious editorial aid and careful typing of the manuscript.
    Type of Medium: Electronic Resource
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