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Senadhi Vijay-Kumar

Bio: Senadhi Vijay-Kumar is an academic researcher from University of Alabama at Birmingham. The author has contributed to research in topics: Calmodulin & Protein structure. The author has an hindex of 11, co-authored 14 publications receiving 2619 citations. Previous affiliations of Senadhi Vijay-Kumar include State University of New York System.

Papers
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Journal ArticleDOI
TL;DR: The crystal structure of human erythrocytic ubiquitin has been refined at 1.8 A resolution using a restrained least-squares procedure and features a number of unusual secondary structural features, including a parallel G1 beta-bulge, two reverse Asx turns, and a symmetrical hydrogen-bonding region that involves the two helices and two of the reverse turns.

1,642 citations

Journal ArticleDOI
03 May 1991-Science
TL;DR: The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques and is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions.
Abstract: The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques. Interferon-gamma, which is dimeric in solution, crystallizes with two dimers related by a noncrystallographic twofold axis in the asymmetric unit. The protein is primarily alpha helical, with six helices in each subunit that comprise approximately 62 percent of the structure; there is no beta sheet. The dimeric structure of human interferon-gamma is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions.

419 citations

Journal ArticleDOI
03 Nov 1989-Science
TL;DR: The complete atomic arrangements within large proteins can only be determined at present using crystallographic techniques, and crystallographic studies have been of major importance for establishing structure/function relationships that are fundamental to understanding how enzymes, nucleic acids, and other macromolecules function in biological systems.
Abstract: The crystals of most proteins or other biological macromolecules are poorly ordered and diffract to lower resolutions than those observed for most crystals of simple organic and inorganic compounds. Crystallization in the microgravity environment of space may improve crystal quality by eliminating convection effects near growing crystal surfaces. A series of 11 different protein crystal growth experiments was performed on U.S. space shuttle flight STS-26 in September 1988. The microgravity-grown crystals of gamma-interferon D1, porcine elastase, and isocitrate lyase are larger, display more uniform morphologies, and yield diffraction data to significantly higher resolutions than the best crystals of these proteins grown on Earth.

165 citations

Journal ArticleDOI
TL;DR: The crystal structure of human ubiquitin has been solved by x-ray diffraction methods and refined by standard procedures to a conventional crystallographic R factor of 0.176 at 1.8-A resolution and difference Fourier electron-density maps reveal that the structures of yeast and oat ubiquitIn are quite similar to human ubiquItin.

141 citations

Journal ArticleDOI
TL;DR: The three-dimensional structure of ubiquitin has been determined at 2.8 A resolution and features include three and one-half turns of alpha-helix, a mixed beta-sheet that contains four strands, and seven reverse turns.
Abstract: The three-dimensional structure of ubiquitin has been determined at 2.8 A resolution. X-ray diffraction data for the native protein and derivatives were collected with an automated diffractometer. Phases were obtained by use of a single isomorphous mercuric acetate derivative. The molecule contains a pronounced hydrophobic core. Prominent secondary structural features include three and one-half turns of alpha-helix, a mixed beta-sheet that contains four strands, and seven reverse turns. The histidine, tyrosine, and two phenylalanine residues are located on the surface of the molecule.

139 citations


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Journal ArticleDOI
TL;DR: Together, these backbone and side chain modifications (hereafter called ff14SB) not only better reproduced their benchmarks, but also improved secondary structure content in small peptides and reproduction of NMR χ1 scalar coupling measurements for proteins in solution.
Abstract: Molecular mechanics is powerful for its speed in atomistic simulations, but an accurate force field is required. The Amber ff99SB force field improved protein secondary structure balance and dynamics from earlier force fields like ff99, but weaknesses in side chain rotamer and backbone secondary structure preferences have been identified. Here, we performed a complete refit of all amino acid side chain dihedral parameters, which had been carried over from ff94. The training set of conformations included multidimensional dihedral scans designed to improve transferability of the parameters. Improvement in all amino acids was obtained as compared to ff99SB. Parameters were also generated for alternate protonation states of ionizable side chains. Average errors in relative energies of pairs of conformations were under 1.0 kcal/mol as compared to QM, reduced 35% from ff99SB. We also took the opportunity to make empirical adjustments to the protein backbone dihedral parameters as compared to ff99SB. Multiple sm...

6,367 citations

Journal ArticleDOI
15 Nov 2006-Proteins
TL;DR: An effort to improve the φ/ψ dihedral terms in the ff99 energy function achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data.
Abstract: The ff94 force field that is commonly associated with the Amber simulation package is one of the most widely used parameter sets for biomolecular simulation. After a decade of extensive use and testing, limitations in this force field, such as over-stabilization of alpha-helices, were reported by us and other researchers. This led to a number of attempts to improve these parameters, resulting in a variety of "Amber" force fields and significant difficulty in determining which should be used for a particular application. We show that several of these continue to suffer from inadequate balance between different secondary structure elements. In addition, the approach used in most of these studies neglected to account for the existence in Amber of two sets of backbone phi/psi dihedral terms. This led to parameter sets that provide unreasonable conformational preferences for glycine. We report here an effort to improve the phi/psi dihedral terms in the ff99 energy function. Dihedral term parameters are based on fitting the energies of multiple conformations of glycine and alanine tetrapeptides from high level ab initio quantum mechanical calculations. The new parameters for backbone dihedrals replace those in the existing ff99 force field. This parameter set, which we denote ff99SB, achieves a better balance of secondary structure elements as judged by improved distribution of backbone dihedrals for glycine and alanine with respect to PDB survey data. It also accomplishes improved agreement with published experimental data for conformational preferences of short alanine peptides and better accord with experimental NMR relaxation data of test protein systems.

6,146 citations

Journal ArticleDOI
TL;DR: A review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena as mentioned in this paper.
Abstract: Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

4,044 citations

Journal ArticleDOI
TL;DR: The current understanding of IFN‐γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophages function during infection are reviewed.
Abstract: Interferon-gamma (IFN-gamma) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-gamma ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-gamma signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-gamma are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-alpha, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.

3,589 citations

Journal ArticleDOI
TL;DR: The results indicate that the revised CHARMM 36 parameters represent an improved model for the modeling and simulation studies of proteins, including studies of protein folding, assembly and functionally relevant conformational changes.
Abstract: While the quality of the current CHARMM22/CMAP additive force field for proteins has been demonstrated in a large number of applications, limitations in the model with respect to the equilibrium between the sampling of helical and extended conformations in folding simulations have been noted. To overcome this, as well as make other improvements in the model, we present a combination of refinements that should result in enhanced accuracy in simulations of proteins. The common (non Gly, Pro) backbone CMAP potential has been refined against experimental solution NMR data for weakly structured peptides, resulting in a rebalancing of the energies of the α-helix and extended regions of the Ramachandran map, correcting the α-helical bias of CHARMM22/CMAP. The Gly and Pro CMAPs have been refitted to more accurate quantum-mechanical energy surfaces. Side-chain torsion parameters have been optimized by fitting to backbone-dependent quantum-mechanical energy surfaces, followed by additional empirical optimization targeting NMR scalar couplings for unfolded proteins. A comprehensive validation of the revised force field was then performed against data not used to guide parametrization: (i) comparison of simulations of eight proteins in their crystal environments with crystal structures; (ii) comparison with backbone scalar couplings for weakly structured peptides; (iii) comparison with NMR residual dipolar couplings and scalar couplings for both backbone and side-chains in folded proteins; (iv) equilibrium folding of mini-proteins. The results indicate that the revised CHARMM 36 parameters represent an improved model for the modeling and simulation studies of proteins, including studies of protein folding, assembly and functionally relevant conformational changes.

3,421 citations