Basic life sciences最新文献

{"title":"Determination of protein and solvent volumes in protein crystals from contrast variation data.","authors":"J Badger","doi":"10.1007/978-1-4615-5847-7_29","DOIUrl":"https://doi.org/10.1007/978-1-4615-5847-7_29","url":null,"abstract":"<p><p>By varying the relative values of protein and solvent scattering densities in a crystal, it is possible to obtain information on the shape and dimensions of protein molecular envelopes. Neutron diffraction methods are ideally suited to these contrast variation experiments because H/D exchange leads to large differential changes in the protein and solvent scattering densities and is structurally non-perturbing. Low resolution structure factors have been measured from cubic insulin crystals with differing H/D contents. Structure factors calculated from a simple binary density model, in which uniform scattering densities represent the protein and solvent volumes in the crystals, were compared with these data. The contrast variation differences in the sets of measured structure factors were found to be accurately fitted by this simple model. Trial applications to two problems in crystal structure determination illustrate how this fact may be exploited. (i) A translation function that employs contrast variation data gave a sharp minimum within 1-9A of the correctly positioned insulin molecule and is relatively insensitive to errors in the atomic model. (ii) An ab initio phasing method for the contrast variation data, based on analyzing histograms of the density distributions in trial maps, was found to recover the correct molecular envelope.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"64 ","pages":"333-43"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19988974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-of-flight Laue fiber diffraction studies of perdeuterated DNA.","authors":"V T Forsyth,&nbsp;P Langan,&nbsp;M A Whalley,&nbsp;A Mahendrasingam,&nbsp;C C Wilson,&nbsp;U Giesen,&nbsp;M T Dauvergne,&nbsp;S A Mason,&nbsp;W Fuller","doi":"10.1007/978-1-4615-5847-7_31","DOIUrl":"https://doi.org/10.1007/978-1-4615-5847-7_31","url":null,"abstract":"<p><p>The diffractometer SXD at the Rutherford Appleton Laboratory ISIS pulsed neutron source has been used to record high resolution time-of-flight Laue fiber diffraction data from DNA. These experiments, which are the first of their kind, were undertaken using fibers of DNA in the A conformation and prepared using deuterated DNA in order to minimise incoherent background scattering. These studies complement previous experiments on instrument D19 at the Institut Laue Langevin using monochromatic neutrons. Sample preparation involved drawing large numbers of these deuterated DNA fibers and mounting them in a parallel array. The strategy of data collection is discussed in terms of camera design, sample environment and data collection. The methods used to correct the recorded time-of-flight data and map it into the final reciprocal space fiber diffraction dataset are also discussed. Difference Fourier maps showing the distribution of water around A-DNA calculated on the basis of these data are compared with results obtained using data recorded from hydrogenated A-DNA on D19. Since the methods used for sample preparation, data collection and data processing are fundamentally different for the monochromatic and Laue techniques, the results of these experiments also afford a valuable opportunity to independently test the data reduction and analysis techniques used in the two methods.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"64 ","pages":"359-67"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19988976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-angle neutron scattering instrument of institute for solid state physics, the University of Tokyo (SANS-U) and its application to biology.","authors":"Y Ito,&nbsp;M Imai,&nbsp;S Takahashi","doi":"10.1007/978-1-4615-5847-7_12","DOIUrl":"https://doi.org/10.1007/978-1-4615-5847-7_12","url":null,"abstract":"<p><p>A small-angle neutron spectrometer (SANS-U) suitable for the study of mesoscopic structure in the field of polymer chemistry and biology, has been constructed at the guide hall of JRR-3M reactor at the Japan Atomic Energy Research Institute. The instrument is 32m long and utilizes a mechanical velocity selector and pinhole collimation to provide a continuous beam with variable wavelength in the range from 5 to 10 A. The neutron detector is a 65 x 65 cm2 2D position sensitive proportional counter. The practical Q range of SANS-U is 0.0008 to 0.45 A-1. The design, characteristics and performance of SANS-U are described with some biological studies using SANS-U.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"64 ","pages":"115-26"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19990331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A neutron image plate quasi-Laue diffractometer for protein crystallography.","authors":"F Cipriani,&nbsp;J C Castagna,&nbsp;C Wilkinson,&nbsp;M S Lehmann,&nbsp;G Büldt","doi":"10.1007/978-1-4615-5847-7_36","DOIUrl":"https://doi.org/10.1007/978-1-4615-5847-7_36","url":null,"abstract":"<p><p>An instrument which is based on image plate technology has been constructed to perform cold neutron Laue crystallography on protein structures. The crystal is mounted at the center of a cylindrical detector which is 400mm long and has a circumference of 1000mm, with gadolinium oxide-containing image plates mounted on its exterior surface. Laue images registered on the plate are read out by rotating the drum and translating a laser read head parallel to the cylinder axis, giving a pixel size of 200 microm x 200 microm and a total read time of 5 minutes. Preliminary results indicate that it should be possible to obtain a complete data set from a protein crystal to atomic resolution in about two weeks.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"64 ","pages":"423-31"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20043478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxyl and water molecule orientations in trypsin: comparison to molecular dynamic structures.","authors":"R S McDowell,&nbsp;A A Kossiakoff","doi":"10.1007/978-1-4615-5847-7_24","DOIUrl":"https://doi.org/10.1007/978-1-4615-5847-7_24","url":null,"abstract":"<p><p>A comparison is presented of experimentally observed hydroxyl and water hydrogens in trypsin determined from neutron density maps with the results of a 140ps molecular dynamics (MD) simulation. Experimental determination of hydrogen and deuterium atom positions in molecules as large as proteins is a unique capability of neutron diffraction. The comparison addresses the degree to which a standard force-field approach can adequately describe the local electrostatic and van der Waals forces that determine the orientations of these hydrogens. The molecular dynamics simulation, based on the all-atom AMBER force-field, allowed free rotation of all hydroxyl groups and movement of water molecules making up a bath surrounding the protein. The neutron densities, derived from 2.1A D2O-H2O difference Fourier maps, provide a database of 27 well-ordered hydroxyl hydrogens. Virtually all of the simulated hydroxyl orientations are within a standard deviation of the experimentally-observed positions, including several examples in which both the simulation and the neutron density indicate that a hydroxyl group is shifted from a 'standard' rotamer. For the most highly ordered water molecules, the hydrogen distributions calculated from the trajectory were in good agreement with neutron density; simulated water molecules that displayed multiple hydrogen bonding networks had correspondingly broadened neutron density profiles. This comparison was facilitated by development of a method to construct a pseudo 2A density map based on the hydrogen atom distributions from the simulation. The degree of internal water molecules is shown to result primarily from the electrostatic environment surrounding that water molecule as opposed to the cavity size available to the molecule. A method is presented for comparing the discrete observations sampled in a dynamics trajectory with the time-averaged data obtained from X-ray or neutron diffraction studies. This method is particularly useful for statically-disordered water molecules, in which the average location assigned from a trajectory may represent a site of relatively low occupancy.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"64 ","pages":"273-87"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20043569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational biology opportunity and challenges for the future.","authors":"J C Wooley,&nbsp;M N Varma","doi":"10.1007/978-1-4757-9788-6_1","DOIUrl":"https://doi.org/10.1007/978-1-4757-9788-6_1","url":null,"abstract":"<p><p>Recent developments in high performance computers and computing methods have opened new avenues for tackling serious, important and challenging problems in biology and medicine. Only a few years back these problems were considered too complex and difficult, if not impossible to solve. An understanding of cross-disciplinary knowledge will be a prerequisite for applications of this enormous computing capability to enhance our understanding of governing principals in biology and medicine. We will show some specific research areas where computational biology can be applied effectively and then provide some ideas on future applications.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"63 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18756909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct ionization of DNA in solution.","authors":"J H Miller,&nbsp;W E Wilson,&nbsp;R H Ritchie","doi":"10.1007/978-1-4757-9788-6_6","DOIUrl":"https://doi.org/10.1007/978-1-4757-9788-6_6","url":null,"abstract":"<p><p>Most of the energy absorbed in the cell nucleus from a radiation field goes into the aqueous medium that surrounds macromolecules, like DNA, which are critical to the normal function of cells. This part of the energy deposition produces numerous reactive species that can diffuse to DNA sequences and induce chemical changes. The average diffusion distance of the free radicals that mediate this indirect mode of DNA damage is only a few nanometers because the cellular medium contains a high concentration of molecules that rapidly scavenge the radiation-induced species. Under these conditions, direct interaction of the radiation field with the DNA can not be neglected as a potential mode of damage induction. Two aspects of the direct effect will be discussed in this paper: (1) screening of the interaction between DNA and charged particles by the dielectric response of the aqueous medium and (2) the impact-parameter dependence of these interactions.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"63 ","pages":"65-74; discussion 74-6"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-1-4757-9788-6_6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18758097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of significant challenges in molecular biology amenable to computational methods.","authors":"R M Glaeser","doi":"10.1007/978-1-4757-9788-6_2","DOIUrl":"https://doi.org/10.1007/978-1-4757-9788-6_2","url":null,"abstract":"<p><p>Many challenging but significant opportunities exist for the development of theoretical approaches in modern Cell and Molecular Biology. The creation of data bases which contain extremely large amounts of information has proven to be an unexpectedly important facto-tin gaining acceptance and respectability for theoretical work that builds on nothing more than what is in the data base itself, such as theoretical work involving the analysis of known protein structures, or the development of more powerful homology searches. Other opportunities, not yet accepted by a broad community, involve work on complex networks (metabolic, genetic, immunologic and neural networks) and work on the \"physics of how things work.\" The DOE National Laboratory System represents the ideal institution that would be well suited to the role of being an \"incubator\" for the creation of a theoretical and computational discipline within modern biology.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"63 ","pages":"11-8; discussion 18-9"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18758090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three statistical technologies with high potential in biological imaging and modeling.","authors":"M Fridman,&nbsp;J M Steele","doi":"10.1007/978-1-4757-9788-6_15","DOIUrl":"https://doi.org/10.1007/978-1-4757-9788-6_15","url":null,"abstract":"<p><p>The three technologies that are surveyed here are (1) wavelet approximations, (2) hidden Markov models, and (3) the Markov chain Renaissance. The intention of the article is to provide an introduction to the benefits these technologies offer and to explain as far as possible the sources of their effectiveness. We also hope to suggest some useful relationships between these technologies and issues of importance on the agenda of biological and medical research.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"63 ","pages":"199-224"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18758093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Track structure, chromosome geometry and chromosome aberrations.","authors":"D J Brenner,&nbsp;J F Ward,&nbsp;R K Sachs","doi":"10.1007/978-1-4757-9788-6_8","DOIUrl":"https://doi.org/10.1007/978-1-4757-9788-6_8","url":null,"abstract":"<p><p>The joint role of radiation track structure and chromosome geometry in determining yields of chromosome aberrations is discussed. Ideally, the geometric models of chromosomes used for analyzing aberration yields should have the same degree of realism as track structure models. However, observed chromosome aberrations are produced by processes on comparatively large scales, e.g., misrepair involving two DSB located on different chromosomes or two DSB separated by millions of base pairs on one chromosome, and quantitative models for chromatin on such large scales have to date almost never been attempted. We survey some recent data on large-scale chromosome geometry, mainly results obtained with fluorescence in situ hybridization (\"chromosome painting\") techniques. Using two chromosome models suggested by the data, we interpret the relative yields, at low and high LET, of inter-chromosomal aberrations compared to intra-chromosomal, inter-arm aberrations. The models consider each chromosome confined within its own \"chromosome localization sphere,\" either as a random cloud of points in one model or as a confined Gaussian polymer in the other. In agreement with other approaches, our results indicate that at any given time during the G0/G1 part of the cell cycle a chromosome is largely confined to a sub-volume comprising less than 10% of the volume of the cell nucleus. The possible significance of the ratio of inter-chromosomal aberrations to intra-chromosomal, inter-arm aberrations as an indicator of previous exposure to high LET radiation is outlined.</p>","PeriodicalId":8697,"journal":{"name":"Basic life sciences","volume":"63 ","pages":"93-109; discussion 109-13"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/978-1-4757-9788-6_8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18756141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}