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Multi-wavelength Anomalous Diffraction
Multi-wavelength anomalous diffraction (sometimes Multi-wavelength anomalous dispersion; abbreviated MAD) is a technique used in X-ray crystallography that facilitates the determination of the three-dimensional structure of biological macromolecules (e.g. DNA, drug receptors) via solution of the phase problem. MAD was developed by Wayne Hendrickson while working as a postdoctoral researcher under Jerome Karle at the United States Naval Research Laboratory. The mathematics upon which MAD (and progenitor Single wavelength anomalous dispersion) were based were developed by Jerome Karle, work for which he was awarded the 1985 Nobel Prize in Chemistry (along with Herbert Hauptman). See also * Single wavelength anomalous dispersion (SAD) * Multiple isomorphous replacement (MIR) *Anomalous scattering *Anomalous X-ray scattering Anomalous X-ray scattering (AXRS or XRAS) is a non-destructive determination technique within X-ray diffraction that makes use of the anomalous dispersion that o ...
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X-ray Crystallography
X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles and intensities of these diffracted beams, a crystallographer can produce a three-dimensional picture of the density of electrons within the crystal. From this electron density, the mean positions of the atoms in the crystal can be determined, as well as their chemical bonds, their crystallographic disorder, and various other information. Since many materials can form crystals—such as salts, metals, minerals, semiconductors, as well as various inorganic, organic, and biological molecules—X-ray crystallography has been fundamental in the development of many scientific fields. In its first decades of use, this method determined the size of atoms, the lengths and types of chemical bonds, and the atomic-scale differences among variou ...
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Phase Problem
In physics, the phase problem is the problem of loss of information concerning the phase that can occur when making a physical measurement. The name comes from the field of X-ray crystallography, where the phase problem has to be solved for the determination of a structure from diffraction data. The phase problem is also met in the fields of imaging and signal processing. Various approaches of phase retrieval have been developed over the years. Overview Light detectors, such as photographic plates or CCDs, measure only the intensity of the light that hits them. This measurement is incomplete (even when neglecting other degrees of freedom such as polarization and angle of incidence) because a light wave has not only an amplitude (related to the intensity), but also a phase (related to the direction), and polarization which are systematically lost in a measurement. In diffraction or microscopy experiments, the phase part of the wave often contains valuable information on the st ...
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Wayne Hendrickson
Wayne A. Hendrickson (born April 25, 1941, New York City) is an American biophysicist and University professor at Columbia. Dr. Hendrickson is a University Professor at Columbia University in the Department of Biochemistry and Molecular Biophysics and Violin Family Professor of Physiology and Cellular Biophysics. He is also Chief Life Scientist in the Photon Sciences Directorate at Brookhaven National Laboratory and Scientific Director of the New York Structural Biology Center. Hendrickson has a B.A. from the University of Wisconsin at River Falls, a Ph.D. in biophysics at Johns Hopkins University with Warner Love, and postdoctoral research experience with Jerome Karle at the Naval Research Laboratory (NRL). He and his colleagues use biochemistry and x-ray crystallography to study molecular properties in atomic detail with current emphasis on membrane receptors and cellular signaling, on viral proteins and HIV infection, on molecular chaperones and protein folding, and on structural ...
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Postdoctoral Research
A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). The ultimate goal of a postdoctoral research position is to pursue additional research, training, or teaching in order to have better skills to pursue a career in academia, research, or any other field. Postdocs often, but not always, have a temporary academic appointment, sometimes in preparation for an academic faculty position. They continue their studies or carry out research and further increase expertise in a specialist subject, including integrating a team and acquiring novel skills and research methods. Postdoctoral research is often considered essential while advancing the scholarly mission of the host institution; it is expected to produce relevant publications in peer-reviewed academic journals or conferences. In some countries, postdoctoral research may lead to further formal qualification ...
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Jerome Karle
Jerome Karle (born Jerome Karfunkle; June 18, 1918 – June 6, 2013) was an American physical chemist. Jointly with Herbert A. Hauptman, he was awarded the Nobel Prize in Chemistry in 1985, for the direct analysis of crystal structures using X-ray scattering techniques.NRL Scientists Receive 1985 Nobel Prize in Chemistry
, . Accessed September 22, 2009.
W.A. Hendrickson (2013) ''Jerome Karle (1918–2013)'', 499(7459), pp 410. < ...
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United States Naval Research Laboratory
The United States Naval Research Laboratory (NRL) is the corporate research laboratory for the United States Navy and the United States Marine Corps. It was founded in 1923 and conducts basic scientific research, applied research, technological development and prototyping. The laboratory's specialties include plasma physics, space physics, materials science, and tactical electronic warfare. NRL is one of the first US government scientific R&D laboratories, having opened in 1923 at the instigation of Thomas Edison, and is currently under the Office of Naval Research. As of 2016, NRL was a Navy Working Capital Fund activity, which means it is not a line-item in the US Federal Budget. Instead of direct funding from Congress, all costs, including overhead, were recovered through sponsor-funded research projects. NRL's research expenditures were approximately $1 billion per year. Research The Naval Research Laboratory conducts a wide variety of basic research and applied ...
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Single Wavelength Anomalous Dispersion
Single-wavelength anomalous diffraction (SAD) is a technique used in X-ray crystallography that facilitates the determination of the structure of proteins or other biological macromolecules by allowing the solution of the phase problem. In contrast to multi-wavelength anomalous diffraction, SAD uses a single dataset at a single appropriate wavelength. One advantage of the technique is the minimization of time spent in the beam by the crystal, thus reducing potential radiation damage to the molecule while collecting data. SAD is sometimes called "single-wavelength anomalous dispersion", but no dispersive differences are used in this technique since the data are collected at a single wavelength. Today, selenium-SAD is commonly used for experimental phasing due to the development of methods for selenomethionine incorporation into recombinant proteins. See also * Multi-wavelength anomalous dispersion (MAD) * Multiple isomorphous replacement (MIR) *Anomalous scattering *Anomalous X-ray ...
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Nobel Prize In Chemistry
) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "MDCCCXXXIII" above, followed by (smaller) "OB•" then "MDCCCXCVI" below. , awarded_for = Outstanding contributions in chemistry , presenter = Royal Swedish Academy of Sciences , location = Stockholm, Sweden , reward = 9 million SEK (2017) , year = 1901 , holder = Carolyn R. Bertozzi, Morten P. Meldal and Karl Barry Sharpless (2022) , most_awards = Frederick Sanger and Karl Barry Sharpless (2) , website nobelprize.org, previous = 2021 , year2=2022, main=2022, next=2023 The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded ...
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Herbert Hauptman
Herbert Aaron Hauptman (February 14, 1917 – October 23, 2011) was an American mathematician and Nobel laureate. He pioneered and developed a mathematical method that has changed the whole field of chemistry and opened a new era in research in determination of molecular structures of crystallized materials. Today, Hauptman's direct methods, which he continued to improve and refine, are routinely used to solve complicated structures. It was the application of this mathematical method to a wide variety of chemical structures that led the Royal Swedish Academy of Sciences to name Hauptman and Jerome Karle recipients of the 1985 Nobel Prize in Chemistry. Life He was born in to a Jewish family in New York City, the oldest child of Leah (Rosenfeld) and Israel Hauptman. He was married to Edith Citrynell since November 10, 1940, with two daughters, Barbara (1947) and Carol (1950). He was interested in science and mathematics from an early age which he pursued at Townsend Harris High ...
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Multiple Isomorphous Replacement
Multiple isomorphous replacement (MIR) is historically the most common approach to solving the phase problem in X-ray crystallography studies of proteins. For protein crystals this method is conducted by soaking the crystal of a sample to be analyzed with a heavy atom solution or co-crystallization with the heavy atom. The addition of the heavy atom (or ion) to the structure should not affect the crystal formation or unit cell dimensions in comparison to its native form, hence, they should be isomorphic. Data sets from the native and heavy-atom derivative of the sample are first collected. Then the interpretation of the Patterson difference map reveals the heavy atom's location in the unit cell. This allows both the amplitude and the phase of the heavy-atom contribution to be determined. Since the structure factor of the heavy atom derivative (Fph) of the crystal is the vector sum of the lone heavy atom (Fh) and the native crystal (Fp) then the phase of the native Fp and Fph vect ...
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Anomalous Scattering
Anomalous X-ray scattering (AXRS or XRAS) is a non-destructive determination technique within X-ray diffraction that makes use of the anomalous dispersion that occurs when a wavelength is selected that is in the vicinity of an absorption edge of one of the constituent elements of the sample. It is used in materials research to study nanometer sized differences in structure. Atomic scattering factors In X-ray diffraction the scattering factor ''f'' for an atom is roughly proportional to the number of electrons that it possesses. However, for wavelengths that approximate those for which the atom strongly absorbs radiation the scattering factor undergoes a change due to anomalous dispersion. The dispersion not only affects the magnitude of the factor but also imparts a phase shift in the elastic collision of the photon. The scattering factor can therefore best be described as a complex number : f= fo + Δf' + i.Δf" Contrast variation The anomalous aspects of X-ray scattering have b ...
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Anomalous X-ray Scattering
Anomalous X-ray scattering (AXRS or XRAS) is a non-destructive determination technique within X-ray diffraction that makes use of the anomalous dispersion that occurs when a wavelength is selected that is in the vicinity of an absorption edge of one of the constituent elements of the sample. It is used in materials research to study nanometer sized differences in structure. Atomic scattering factors In X-ray diffraction the scattering factor ''f'' for an atom is roughly proportional to the number of electrons that it possesses. However, for wavelengths that approximate those for which the atom strongly absorbs radiation the scattering factor undergoes a change due to anomalous dispersion. The dispersion not only affects the magnitude of the factor but also imparts a phase shift in the elastic collision of the photon. The scattering factor can therefore best be described as a complex number : f= fo + Δf' + i.Δf" Contrast variation The anomalous aspects of X-ray scattering have b ...
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