S. Miller

Bio: S. Miller is an academic researcher from University College London. The author has contributed to research in topics: Ionosphere & Saturn. The author has an hindex of 15, co-authored 33 publications receiving 2398 citations.

The accessible surface area and stability of oligomeric proteins

Abstract: Protein structures are stabilized by hydrophobic and van der Waals forces, and by hydrogen bonds. The relation between these ther-modynamic quantities and the actual three-dimensional structure of proteins can not be calculated precisely. However, certain empirical relations have been discovered. Hydrophobic energy is gained by the reduction of surface in contact with water1. For monomeric proteins, the area of the surface accessible to solvent, and of that buried in the interior, is a simple function of molecular weight. Proteins with different shapes and secondary structures, but of the same molecular weight, have the same accessible surface area2–5. It has been argued that there is no similar relationship for large oligomeric proteins6. In this paper we show that the surface areas of oligomeric proteins, and the areas of the surface buried within them, are directly related to relative molecular mass. Although oligomers of the same molecular weight bury the same amounts of surface, the proportions buried within and between subunits vary. This has important implications for the role of subunit interfaces in the stability and activity of oligomeric proteins.

Methane in the atmosphere of the transiting hot Neptune GJ436b

Abstract: We present an analysis of seven primary transit observations of the hot Neptune GJ436b at 3.6, 4.5 and $8~\mu$m obtained with the Infrared Array Camera (IRAC) on the Spitzer Space Telescope. After correcting for systematic effects, we fitted the light curves using the Markov Chain Monte Carlo technique. Combining these new data with the EPOXI, HST and ground-based $V, I, H$ and $K_s$ published observations, the range $0.5-10~\mu$m can be covered. Due to the low level of activity of GJ436, the effect of starspots on the combination of transits at different epochs is negligible at the accuracy of the dataset. Representative climate models were calculated by using a three-dimensional, pseudo-spectral general circulation model with idealised thermal forcing. Simulated transit spectra of GJ436b were generated using line-by-line radiative transfer models including the opacities of the molecular species expected to be present in such a planetary atmosphere. A new, ab-initio calculated, linelist for hot ammonia has been used for the first time. The photometric data observed at multiple wavelengths can be interpreted with methane being the dominant absorption after molecular hydrogen, possibly with minor contributions from ammonia, water and other molecules. No clear evidence of carbon monoxide and dioxide is found from transit photometry. We discuss this result in the light of a recent paper where photochemical disequilibrium is hypothesised to interpret secondary transit photometric data. We show that the emission photometric data are not incompatible with the presence of abundant methane, but further spectroscopic data are desirable to confirm this scenario.

The domination of Saturn’s low-latitude ionosphere by ring ‘rain’

Abstract: A pattern of features is detected, superposed on Saturn’s low-latitude infrared glow, that implies the transfer of charged species derived from water (ring ‘rain’) from the ring plane to the ionosphere, ultimately leading to the global modulation of upper atmospheric chemistry. A magnetic connection between Saturn and its ring system has been suggested previously. It might explain, among other things, the unexpectedly low electron densities and high temperatures observed in the ionosphere. Now that missing link has been observed. Near-infrared spectral data from the W. M. Keck II telescope, focused on Saturn's noon meridian, are consistent with the transfer of charged water from the rings to the ionosphere, sufficient to flood a third of the planet's upper atmospheric surface. This ring 'rain' links the rings to the planet electrically and magnetically, leading to the global modulation of upper atmospheric chemistry. Saturn’s ionosphere is produced when the otherwise neutral atmosphere is exposed to a flow of energetic charged particles or solar radiation1. At low latitudes the solar radiation should result in a weak planet-wide glow in the infrared, corresponding to the planet’s uniform illumination by the Sun2. The observed electron density of the low-latitude ionosphere, however, is lower and its temperature higher than predicted by models3,4,5. A planet-to-ring magnetic connection has been previously suggested, in which an influx of water from the rings could explain the lower-than-expected electron densities in Saturn’s atmosphere6,7,8. Here we report the detection of a pattern of features, extending across a broad latitude band from 25 to 60 degrees, that is superposed on the lower-latitude background glow, with peaks in emission that map along the planet’s magnetic field lines to gaps in Saturn’s rings. This pattern implies the transfer of charged species derived from water from the ring-plane to the ionosphere, an influx on a global scale, flooding between 30 to 43 per cent of the surface of Saturn’s upper atmosphere. This ring ‘rain’ is important in modulating ionospheric emissions and suppressing electron densities.

Hydrogen Bonding in Biological Structures

Abstract: IA Basic Concepts.- 1 The Importance of Hydrogen Bonds.- 1.1 Historical Perspective.- 1.2 The Importance of Hydrogen Bonds in Biological Structure and Function.- 1.3 The Role of the Water Molecules.- 1.4 Significance of Small Molecule Crystal Structural Studies.- 1.5 The Structural Approach.- 2 Definitions and Concepts.- 2.1 Definition of the Hydrogen Bond - Strong and Weak Bonds.- 2.2 Hydrogen-Bond Configurations: Two- and Three-Center Hydrogen Bonds Bifurcated and Tandem Bonds.- 2.3 Hydrogen Bonds Are Very Different from Covalent Bonds.- 2.4 The van der Waals Radii Cut-Off Criterion Is Not Useful.- 2.5 The Concept of the Hydrogen-Bond Structure.- 2.6 The Importance of ? and ? Cooperativity.- 2.7 Homo-, Anti- and Heterodromic Patterns.- 2.8 Hydrogen Bond Flip-Flop Disorder: Conformational and Configurational.- 2.9 Proton-Deficient Hydrogen Bonds.- 2.10 The Excluded Region.- 2.11 The Hydrophobic Effect.- 3 Experimental Studies of Hydrogen Bonding.- 3.1 Infrared Spectroscopy and Gas Electron Diffraction.- 3.2 X-Ray and Neutron Crystal Structure Analysis.- 3.3 Treatment of Hydrogen Atoms in Neutron Diffraction Studies.- 3.4 Charge Density and Hydrogen-Bond Energies.- 3.5 Neutron Powder Diffraction.- 3.6 Solid State NMR Spectroscopy.- 4 Theoretical Calculations of Hydrogen-Bond Geometries.- 4.1 Calculating Hydrogen-Bond Geometries.- 4.2 Ab-Initio Molecular Orbital Methods.- 4.3 Application to Hydrogen-Bonded Complexes.- 4.4 Semi-Empirical Molecular Orbital Methods.- 4.5 Empirical Force Field or Molecular Mechanics Methods.- 5 Effect of Hydrogen Bonding on Molecular Structure.- IB Hydrogen-Bond Geometry.- 6 The Importance of Small Molecule Structural Studies.- 6.1 Problems Associated with the Hydrogen-Bond Geometry.- 6.2 The Hydrogen Bond Can Be Described Statistically.- 6.3 The Problems of Measuring Hydrogen-Bond Lengths and Angles in Small Molecule Crystal Structures.- 7 Metrical Aspects of Two-Center Hydrogen Bonds.- 7.1 The Metrical Properties of O-H *** O Hydrogen Bonds.- 7.1.1 Very Strong and Strong OH *** O Hydrogen Bonds Occur with Oxyanions, Acid Salts, Acid Hydrates, and Carboxylic Acids.- 7.1.2 OH *** O Hydrogen Bonds in the Ices and High Hydrates.- 7.1.3 Carbohydrates Provide the Best Data for OH ... O Hydrogen Bonds: Evidence for the Cooperative Effect.- 7.2 N-H *** O Hydrogen Bonds.- 7.3 N-H *** N Hydrogen Bonds.- 7.4 O-H *** N Hydrogen Bonds.- 7.5 Sequences in Lengths of Two-Center Hydrogen Bonds.- 7.6 H/D Isotope Effect.- 8 Metrical Aspects of Three- and Four-Center Hydrogen Bonds.- 8.1 Three-Center Hydrogen Bonds.- 8.2 Four-Center Hydrogen Bonds.- 9 Intramolecular Hydrogen Bonds.- 10 Weak Hydrogen-Bonding Interactions Formed by C-H Groups as Donors and Aromatic Rings as Acceptors.- 11 Halides and Halogen Atoms as Hydrogen-Bond Acceptors.- 12 Hydrogen-Bond Acceptor Geometries.- II Hydrogen Bonding in Small Biological Molecules.- 13 Hydrogen Bonding in Carbohydrates.- 13.1 Sugar Alcohols (Alditols) as Model Cooperative Hydrogen-Bonded Structures.- 13.2 Influence of Hydrogen Bonding on Configuration and Conformation in Cyclic Monosaccharides.- 13.3 Rules to Describe Hydrogen-Bonding Patterns in Monosaccharides.- 13.4 The Water Molecules Link Hydrogen-Bond Chains into Nets in the Hydrated Monosaccharide Crystal Structures.- 13.5 The Disaccharide Crystal Structures Provide an Important Source of Data About Hydrogen-Bonding Patterns in Polysaccharides.- 13.6 Hydrogen Bonding in the Tri- and Tetrasaccharides Is More Complex and Less Well Defined.- 13.7 The Hydrogen Bonding in Polysaccharide Fiber Structures Is Poorly Defined.- 14 Hydrogen Bonding in Amino Acids and Peptides: Predominance of Zwitterions.- 15 Purines and Pyrimidines.- 15.1 Bases Are Planar and Each Contains Several Different Hydrogen-Bonding Donor and Acceptor Groups.- 15.2 Many Tautomeric Forms Are Feasible But Not Observed.- 15.3 ?-Bond Cooperativity Enhances Hydrogen-Bonding Forces.- 15.4 General, Non-Base-Pairing Hydrogen Bonds.- 16 Base Pairing in the Purine and Pyrimidine Crystal Structures.- 16.1 Base-Pair Configurations with Purine and Pyrimidine Homo-Association.- 16.2 Base-Pair Configurations with Purine-Pyrimidine Hetero-Association: the Watson-Crick Base-Pairs.- 16.3 Base Pairs Can Combine to Form Triplets and Quadruplets.- 17 Hydrogen Bonding in the Crystal Structures of the Nucleosides and Nucleotides.- 17.1 Conformational and Hydrogen-Bonding Characteristics of the Nucleosides and Nucleotides.- 17.2 A Selection of Cyclic Hydrogen-Bonding Patterns Formed in Nucleoside and Nucleotide Crystal Structures.- 17.3 General Hydrogen-Bonding Patterns in Nucleoside and Nucleotide Crystal Structures.- III Hydrogen Bonding in Biological Macromolecules.- 18 O-H *** O Hydrogen Bonding in Crystal Structures of Cyclic and Linear Oligoamyloses: Cyclodextrins, Maltotriose, and Maltohexaose.- 18.1 The Cyclodextrins and Their Inclusion Complexes.- 18.2 Crystal Packing Patterns of Cyclodextrins Are Determined by Hydrogen Bonding.- 18.3 Cyclodextrins as Model Compounds to Study Hydrogen-Bonding Networks.- 18.4 Cooperative, Homodromic, and Antidromic Hydrogen-Bonding Patterns in the ?-Cyclodextrin Hydrates.- 18.5 Homodromic and Antidromic O-H *** O Hydrogen-Bonding Systems Analyzed Theoretically.- 18.6 Intramolecular Hydrogen Bonds in the ?-Cyclodextrin Molecule are Variable - the Induced-Fit Hypothesis.- 18.7 Flip-Flop Hydrogen Bonds in ?-Cyclodextrin * 11 H2O.- 18.8 From Flip-Flop Disorder to Ordered Homodromic Arrangements at Low lbmperature: The Importance of the Cooperative Effect.- 18.9 Maltohexaose Polyiodide and Maltotriose - Double and Single Left-Handed Helices With and Without Intramolecular O(2) *** O(3?) Hydrogen Bonds.- 19 Hydrogen Bonding in Proteins.- 19.1 Geometry of Secondary-Structure Elements: Helix, Pleated Sheet, and Turn.- 19.2 Hydrogen-Bond Analysis in Protein Crystal Structures.- 19.3 Hydrogen-Bonding Patterns in the Secondary Structure Elements.- 19.4 Hydrogen-Bonding Patterns Involving Side-Chains.- 19.5 Internal Water Molecules as Integral Part of Protein Structures.- 19.6 Metrical Analysis of Hydrogen Bonds in Proteins.- 19.7 Nonsecondary-Structure Hydrogen-Bond Geometry Between Main-Chains, Side-Chains and Water Molecules.- 19.8 Three-Center (Bifurcated) Bonds in Proteins.- 19.9 Neutron Diffraction Studies on Proteins Give Insight into Local Hydrogen-Bonding Flexibility.- 19.10 Site-Directed Mutagenesis Gives New Insight into Protein Thermal Stability and Strength of Hydrogen Bonds.- 20 The Role of Hydrogen Bonding in the Structure and Function of the Nucleic Acids.- 20.1 Hydrogen Bonding in Nucleic Acids is Essential for Life.- 20.2 The Structure of DNA and RNA Double Helices is Determined by Watson-Crick Base-Pair Geometry.- 20.3 Systematic and Accidental Base-Pair Mismatches: "Wobbling" and Mutations.- 20.4 Noncomplementary Base Pairs Have a Structural Role in tRNA.- 20.5 Homopolynucleotide Complexes Are Stabilized by a Variety of Base-Base Hydrogen Bonds - Three-Center (Bifurcated) Hydrogen Bonds in A-Tracts.- 20.6 Specific Protein-Nucleic Acid Recognition Involves Hydrogen Bonding.- IV Hydrogen Bonding by the Water Molecule.- 21 Hydrogen-Bonding Patterns in Water, Ices, the Hydrate Inclusion Compounds, and the Hydrate Layer Structures.- 21.1 Liquid Water and the Ices.- 21.2 The Hydrate Inclusion Compounds.- 21.3 Hydrate Layer Structures.- 22 Hydrates of Small Biological Molecules: Carbohydrates, Amino Acids, Peptides, Purines, Pyrimidines, Nucleosides and Nucleotides.- 23 Hydration of Proteins.- 23.1 Characterization of "Bound Water" at Protein Surfaces - the First Hydration Shell.- 23.2 Sites of Hydration in Proteins.- 23.3 Metrics of Water Hydrogen Bonding to Proteins.- 23.4 Ordered Water Molecules at Protein Surfaces - Clusters and Pentagons.- 24 Hydration of Nucleic Acids.- 24.1 Two Water Layers Around the DNA Double Helix.- 24.2 Crystallographically Determined Hydration Sites in A-, B-, Z-DNA. A Statistical Analysis.- 24.3 Hydration Motifs in Double Helical Nucleic Acids.- 24.3.1 Sequence-Independent Motifs.- 24.3.2 Sequence-Dependent Motifs.- 24.4 DNA Hydration and Structural Transitions Are Correlated: Some Hypotheses.- 25 The Role of Three-Center Hydrogen Bonds in the Dynamics of Hydration and of Structure Transition.- References.- Refcodes.

High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis.

Abstract: A strategy, called alanine-scanning mutagenesis, was used to identify specific side chains in human growth hormone (hGH) that strongly modulate binding to the hGH receptor cloned from human liver. Single alanine mutations (62 in total) were introduced at every residue contained within the three discontinuous segments of hGH (residues 2 to 19, 54 to 74, and 167 to 191) that have been implicated in receptor recognition. The alanine scan revealed a cluster of a dozen large side chains that when mutated to alanine each showed more than a four times lower binding affinity to the hGH receptor. Many of these residues that promote binding to the hGH receptor are altered in homologs of hGH (such as placental lactogens and prolactins) that do not bind tightly to the hGH receptor. The overall folding of these mutant proteins was indistinguishable from that of the wild-type hGH, as determined by strong cross-reactivities with seven different conformationally sensitive monoclonal antibodies. The alanine scan also identified at least one side chain, Glu174, that hindered binding because when it was mutated to alanine the receptor affinity increased by more than a factor of four.