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PubMedDate not supplied

A 1.8 A resolution potential function for protein folding.

A general method is presented for constructing a potential function for approximate conformational calculations on globular proteins. The method involves solving a nonlinear program that seeks to adjust the potential's parameters in such a way that a minimum near the native remains a minimum and does not move far away, while any alternative minima shift so as to remain local minima but eventually rise higher than the level of the near-native minimum. Although the potential trades computational speed for detail by representing each amino acid residue as only a single point, correct secondary structural preferences and reasonable tertiary folding can be built into the potential in an entirely routine way. The potential has been parameterized to agree with the crystal structure of avian pancreatic polypeptide (having 36 residues) in the sense that the lowest minimum found (-407 arbitrary units) is reasonably close to the native (1.8 A rms interresidue distance deviation). In contrast, the lowest nonnative conformation found after extensive searches by a variety of methods was -399 units and 7.5 A away. Such potentials may prove to be useful in predicting approximate tertiary structure from amino acid sequence, if they can be generalized to apply to more than one protein.

Methods↗
PubMed2004

Development of softcore potential functions for overcoming steric barriers in molecular dynamics simulations.

In this work, we describe the development of softcore potential functions that permit occasional "tunneling" through the regions of conformational space during molecular dynamics (MD) simulations, which would otherwise be sterically prohibited. The modification consists of a truncation of the nonbonded interaction before the steeply repulsive region encountered at short interatomic distances. This modification affects both Lennard-Jones and Coulomb parts of the nonbonded potential. Critical to success is the choice of appropriate pairwise switching distances at which this modification should be made. In the present work, these are calculated based on potential of mean force functions extracted from model system molecular dynamics simulations. We believe that these functions describe the dynamic short-range interactions much better than mean force potentials derived from an ensemble of static structures (e.g. protein data bank (PDB)). Once a set of mean force potentials is obtained, a single empirical parameter, effective barrier height, is employed to determine switching distances for all pairwise atomic interactions. Changing this single parameter allows adjustment of the "softness" of the whole system. We tested the applicability of the new softcore potentials in a loop structure optimization study. The H1 loop in the antibody 17/9 was selected as our test case because substantial repacking of loop residues in the dense protein environment is necessary for successful relaxation of random initial conformations. Softcore simulations converted to correct loop conformations, in contrast to standard simulations which never sampled this structure even after 10 ns. The resulting root mean square deviation (RMSD) values (below 1.3 A for all heavy atoms of the loop) demonstrate the usefulness of the approach based on mean force derived softcore functions.

Amino Acids↗
PubMed2004

Molecular cloning and functional characterization of a Lepidopteran insect beta4-N-acetylgalactosaminyltransferase with broad substrate specificity, a functional role in glycoprotein biosynthesis, and a potential functional role in glycolipid biosynthesis.

A degenerate PCR approach was used to isolate a lepidopteran insect cDNA encoding a beta4-galactosyl-transferase family member. The isolation and initial identification of this cDNA was based on bioinformatics, but its identification as a beta4-galactosyltransferase family member was experimentally confirmed. The newly identified beta4-galactosyltransferase family member had unusually broad donor and acceptor substrate specificities in vitro, as transferred galactose, N-acetylglucosamine, and N-acetylgalactosamine to carbohydrate, glycoprotein, and glycolipid acceptors. However, the enzyme preferentially utilized N-acetylgalactosamine as the donor for all three acceptors, and its derived amino acid sequence was closely related to a known N-acetylgalactosaminyltransferase. These data suggested that the newly isolated cDNA encodes a beta4-N-acetylgalactosaminyltransferase that functions in insect cell glycoprotein biosynthesis, glycolipid biosynthesis, or both. The remainder of this study focused on the role of this enzyme in N-glycoprotein biosynthesis. The results showed that the purified enzyme transferred N-acetylgalactosamine, but no detectable galactose or N-acetylglucosamine, to a synthetic N-glycan in vitro. The structure of the reaction product was confirmed by chromatographic, mass spectroscopic, and nuclear magnetic resonance analyses. Co-expression of the new cDNA product in insect cells with an N-glycoprotein reporter showed that it transferred N-acetylgalactosamine, but no detectable galactose or N-acetylglucosamine, to this N-glycoprotein in vivo. Confocal microscopy showed that a GFP-tagged version of the enzyme was localized in the insect cell Golgi apparatus. In summary, this study demonstrated that lepidopteran insect cells encode and express a beta4-N-acetylgalactosaminyltransferase that functions in N-glycoprotein biosynthesis and perhaps in glycolipid biosynthesis, as well. The isolation and characterization of this gene and its product contribute to our basic understanding of insect protein N-glycosylation pathways and to the growing body of evidence that insects can produce glycoproteins with complex N-glycans.

Acetylgalactosamine↗
PubMed2003

[The localization and potential function of androgen receptor mRNA in rat submaxillary].

OBJECTIVES: To study the distribution and potential function of androgen receptor (AR) mRNA and AR in rat submaxillary. METHODS: In situ hybridization using digoxigenin-labled oligonucleotide probes, cell culture and radio-immunoassay were performed to localize the AR and detect the concentration of epidermal growth factor (EGF) in culturing supernant. RESULTS: AR mRNA hybridization signals were detected in glandular epithelial cells of serous acinus and epithelial cells in all gland ducts. The signals distributed in cytoplasma of all positive cells with negative nuclei; Administration of testosterone can significantly increase the level of EGF (P < 0.05). CONCLUSIONS: The rat submaxillary not only is a target organ of androgen but also can product AR by itself. When androgen combined with androgen receptor and can submaxillary function can be infected and can result in the elevation of the level of EGF secreted.

Animals↗
PubMed1999

A new Hybrid Monte Carlo algorithm for protein potential function test and structure refinement.

A new Hybrid Monte Carlo (HMC) algorithm has been developed to test protein potential functions and, ultimately, refine protein structures. The main principle of this algorithm is, in each cycle, a new trial conformation is generated by carrying out a short period of molecular dynamics (MD) iterations with a set of random parameters (including the MD time step, the number of MD steps, the MD temperature, and the seed for initial MD velocity assignment); then to accept or reject the new conformation on the basis of the Metropolis criterion. The novelty in this paper is that the potential in MD iterations is different from that in the MC step. In the former, it is a molecular mechanics potential, in the latter it is a knowledge-based potential (KBP). Directed by the KBP, the MD iteration is used to search conformational space for realistic conformations with low KBP energy. It circumvents the difficulty in using KBP functions directly in MD simulation, as KBP functions are typically incomplete, and do not always have continuous derivatives required for the calculation of the forces. The new algorithm has been tested in explorations of conformational space. In these test calculations the KBP energy was found to drop below the value for the native conformation, and the correlation between the root mean square deviation (RMSD) and the KBP energy was shown to be different from the test results in other references. At the present time, the algorithm is useful for testing new KBP functions. Furthermore, if a KBP function can be found for which the native conformation has the lowest energy and the energy/RMSD correlation is good, then this new algorithm also will be a tool for refinement of the theory-based structural models.

Algorithms↗
PubMed1994

Analysis of the functional potential of mouse CD4+ T cells using a high-efficiency cloning system.

In order to examine the functional potential of individual mouse CD4+ T cells selected, as far as possible, in a random manner, a high-efficiency cloning system driven by Con A was utilized. Under optimal conditions, cloning efficiencies of CD4+ cells of about 50% were regularly attained. Although the relative proportion of different TH subsets varied depending on the cloning conditions, the high cloning efficiency, coupled with the analysis of over 100 clones, allowed important conclusions to be drawn regarding the general construction of the mouse CD4+ T cell repertoire. (1) At least 50% of all mouse splenic CD4+ T cells have the potential to produce IL4, supporting the view that TH subsets arise by an instructional or regulatory mechanism, rather than by selection. (2) TH0 clones produce amounts of IL2 and IL4 similar to those produced by TH1 and TH2 clones, respectively, but secrete much lower quantities of IFN than TH1 clones. (3) A large proportion of TH2 clones secrete measurable amounts of IFN. (4) Lymphokine secretion patterns among CD4+ T cells are clearly not determined at random, since IL2 production is always accompanied by IFN production. (5) At least 50% of all mouse splenic CD4+ T cells have cytolytic capacity as shown by killing in a 20-hr assay, but only a proportion can also kill in 4-hr assays. Killing in 4-hr assays was strongly correlated with the ability to secrete IL2, regardless of whether IL4 was also secreted.

Animals↗
PubMed1994

Phi-psi conformational pattern clustering of protein amino acid residues using the potential function method.

This paper describes phi-psi conformational pattern clustering of protein amino acid residues. The method is based on the potential function method and mode seeking technique. phi-psi conformational pattern distribution maps and their three-dimensional potential surface maps were computed for 20 different kinds of amino acid residues, using 67 proteins (14,723 residues) taken from the Protein Data Bank. It was found that glycine residues of proteins have five major clusters in the phi-psi conformational space, and two or three major clusters were found for the other kinds of residues. Mode seeking on the potential surface of glycine residues identified their representative phi-psi conformational patterns: (82.64 degrees, 9.84 degrees), (-62.63 degrees, -41.71 degrees), (-85.33 degrees, 176.78 degrees), (91.88 degrees, 178.14 degrees) and (167.06 degrees, -175.33 degrees). The details of the method and the results are discussed with new classifications of phi-psi conformational patterns of amino acid residues of proteins.

Algorithms↗
PubMed1986

Simulation of interactions between nucleic acid bases by refined atom-atom potential functions.

Energy of interaction between nitrogen bases of nucleic acid has been calculated as a function of parameters determining the mutual position of two bases. Refined atom-atom potential functions are suggested. These functions contain terms proportional to the first (electrostatics), sixth (or tenth for the atoms forming a hydrogen bond) and twelfth (repulsion of all atoms) powers of interatomic distance. Calculations have shown that there are two groups of minima of the base interaction energy. The minima of the first group correspond to coplanar arrangement of the base pairs and hydrogen bond formation. The minima of the second group correspond to the position of bases one above the other in almost parallel planes. There are 28 energy minima corresponding to the formation of coplanar pairs with two (three for the G:C pair) almost linear N-H . . . O and (or) N-H . . . N hydrogen bonds. The position of nitrogen bases paired by two such H-bonds in any crystal of nucleic acid component in polynucleotide complexes and in tRNA is close to the position in one of these minima. Besides, for each pair there are energy minima corresponding to the formation of a single N-H . . . O or N-H . . . N and one C-H . . . O or C-H . . . N hydrogen bond. The form of potential surface in the vicinity of minima has been characterized. The results of calculations agree with the experimental data and with more rigorous calculations based on quantum-mechanical approach.

Base Composition↗
PubMedDate not supplied

[Simulation of interactions in the co-planar nucleic acid base pairs using atom-atom potential functions].

Calculations of the energy of nucleic acid base interactions as a function of parameters determining mutual position of two bases in a plane have been performed. Atom-atom potential functions used include terms proportional to the first (electrostatic), sixth (or tenth for the atoms of hydrogen bond) and 12th power of interatomic distance. The calculations have shown the existence of 27 energy minima which correspond to the formation of co-planar pairs with two (or three for G : C pair) almost linear N--H...O and N--H...N hydrogen bonds. The positions of nitrogen bases bound by two hydrogen bonds in every crystal of nucleic acid components, in the complexes of polynucleotides and in tRNA are near to the positions in one of these minima. In addition for every pair there exist energy minima which correspond to the formation of one N--H...O or N--H...N and one C--H...O or C--H...N hydrogen bond. Energy behavior near minima have been investigated. The results of our calculations are in agreement with experimental data and with the calculations which employ quantum mechanical results.

Base Composition↗
PubMed1989

Delineation of human thymocytes with or without functional potential by CD1-specific antibodies.

Hematopoietic precursors lacking T cell antigen receptors (TCR-CD3-) and CD4 and CD8 surface markers (i.e. double-negative thymocytes) give rise to functionally mature T lymphocytes. Yet their major progeny are immunologically unresponsive thymocytes in spite of having acquired TCR-CD3 and CD4-CD8. Because only mature thymocytes migrate to peripheral lymphoid organs and most thymocytes die in situ, the knowledge of the events associated with functional maturation in the double-negative thymocyte progeny is a fundamental question in T cell development. We reasoned that a clue to trace the fate of early human thymocytes may perhaps come from the study of the developmental acquisition of CD1 antigen, currently used to define better the functionally inert CD4+8+ (double-positive) stage and absent in mature, medullary thymocytes and peripheral T cells. By using antibodies specific for CD1 (HTA 1/T6) we show here that a large fraction of double-negative thymocytes also express CD1. CD1+3-, CD1+3+, CD1-3+, and CD1-3- subsets all exist. The CD1+3- subset generates CD1+3-4-8+ precursors of CD1+ double-positive cells. A large portion of the CD1+3+ subset bears TCR gamma delta-CD3 complexes. The CD1- subsets are responsive in assays of function, in which they can be stimulated to use the interleukin 2 pathway of proliferation and to mediate cytotoxicity. In contrast, all CD1+ thymocytes behave as functionally inert cells. Thus, the CD1 surface marker delineates human thymocyte precursors and their products which lack, or possess, functional potential in vitro, on both alpha beta and gamma delta lineages.

Antibodies, Monoclonal↗
PubMed2003

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.

Alleles↗
PubMed2002

Numerous potentially functional but non-genic conserved sequences on human chromosome 21.

The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes.

Animals↗
PubMed2006

[Impact of photochromotherapy on functional potential of neutrophil granules and adaptive status in children with complicated hemangioma].

Adaptive status was assessed in 50 children. Lysosomal-cationic test was carried out in healthy children and 20 patients with complicated hemangioma. Photochromotherapy was followed by enhanced functional potential of neutrophil granules. That was indicated by greater values of lysosomal-cationic test results as well as by higher counts of high-concentration cationic proteins. Elevated non-specific resistance was accounted for by antistressor reactions.

Antimicrobial Cationic Peptides↗
PubMed2000

Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

Acetic Acid↗
PubMed2026

Bacterial extracellular vesicles exhibit distinct functional potential across biogeographic provinces of the South Pacific Ocean.

Bacterial extracellular vesicles (BEVs) are nanoscale membranous structures released by diverse types of bacteria, and are capable of transporting and delivering biological compounds between cells. Experimental investigation of BEVs in laboratory model systems indicates that these nanoparticles may play a number of roles in the ecophysiology of marine bacterial communities, but their functional potential in the environment remains unclear. Here we describe the proteomic composition of BEV populations over more than 5000 nautical miles of surface waters in the South Pacific, linking BEV cargoes to the bacterial communities producing them. The presence of marine BEVs was consistently observed across a range of biogeochemical conditions, with an overall abundance comparable to that of bacterial cells (up to 108 BEVs L-1). The protein cargo of marine BEVs, however, differed significantly among ocean regions. The BEV populations were enriched in carbohydrate transporters under phytoplankton bloom conditions, and contained iron uptake-related proteins in nutrient-limited waters. These data suggest that BEVs could enable cells to perform key extracellular functions in the marine environment. Our observations highlight the ubiquity of marine BEVs and biogeographic patterns in their ecological potential across oceanic scales.

Extracellular Vesicles↗
PubMed2004

An alternative multipolar expansion for intermolecular potential functions.

We have derived a new multipolar expansion for intermolecular potential-energy functions with applications in molecular physics, theoretical chemistry, and mathematical physics. The new formulation employs a separation of radial and angular terms with a simple index structure that leads to computational efficiency and ease of physical interpretation. For the case of the Coulomb interaction, we compare the present formulation with two conventional multipole expansions: the Cartesian tensor and the irreducible spherical tensor expansions. The new formalism leads to efficient numerical algorithms that are useful for general applications beyond intermolecular potentials. In addition to the electrostatic Coulomb interaction, we illustrate the formalism with applications to special function theory and a bipolar expansion involved in potential theory.

Journal Article↗
PubMed1991

Characterization of potentially functional 5S rRNA-encoding genes within ribosomal DNA repeats of the nematode Meloidogyne arenaria.

In the plant-parasitic nematode Meloidogyne arenaria, isolated rDNA repeats show length heterogeneity, and are unusual in that they contain putative 5S ribosomal RNA pseudogenes [Vahidi et al., J. Mol. Evol. 27 (1988) 222-227]. Potentially functional 5S rRNA-encoding genes can also be identified in various rDNA repeats, which appear to be tandemly organized in the genome.

Animals↗