The orientation of N-H...O=C and N-H...N hydrogen bonds in biological systems: how good is a point charge as a model for a hydrogen bonding atom?

In order to design new ligands for protein-binding sites of unknown structure, it would be useful to predict the likely sites of hydrogen bonding of an unknown protein fragment to a known molecule. The positions of maxima and minima in the electrostatic potential at appropriate distances from the van der Waals surface were calculated for various small molecules, nucleic acid bases, peptide units and amino acid side chains containing groups which can form the biologically important N-H...O=C and N-H...N hydrogen bonds. Their ability to predict the positions of H and O/N in hydrogen bonded complexes, as predicted by optimising the electrostatic interactions of pairs of such molecules constrained by the molecular shapes, was assessed. It is shown that extrema in the electrostatic potential around the isolated molecules give worthwhile predictions for the locations of hydrogen binding partners. For molecules bound by a single N-H...O=C hydrogen bond, the electrostatic maximum associated with the H is usually less than 1 A from an acceptor atom, while a C=O electrostatic minimum is generally less than 1.5 A from the hydrogen bond proton. However, a significant number of hydrogen bonds form to the opposite lone pair from the electrostatic minimum, in which case the separation is up to 3.3 A. This reflects the broad electrostatic potential well around a carbonyl oxygen between the lone pair directions. The model predicts when neighbouring atoms drastically change the hydrogen bonding characteristics of an N-H or C=O group. Although the geometries of hydrogen bonded complexes are influenced by the other van der Waals contacts between the molecules, particularly multiple hydrogen bonds, these influences are constant when considering hydrogen bonding to a specific uncharacterised binding site. Hence, the consideration of sterically accessible electrostatic extrema will be useful in the design of new ligands.     

Molecular arrangements in sphingolipids. Conformation and hydrogen bonding of ceramide and their implication on membrane stability and permeability

The preferred conformation of the ceramide part of sphingolipids has been deduced from single crystal structures of a series of sphingolipid constituents: N-tetracosanoylphytosphingosine, glycosylphytosphingosine hydrochloride, sphingosine hydrochloride, triacetylsphingosine, DL-2-hydroxytetradecanoic acid and N-stearoylethanolamine. The amide group of the ceramide, which serves as a link between the hydrocarbon chains, has a basic significance for the contormation of the entire molecule. This rigid group, which comprises six atoms in a planar conformation, adopts a perpendicular orientation towards the axes of the two hydrocarbon chains. The carbonyl oxygen thereby turns into an eclipsed position with the hydrogen atoma at carbon atom 2 of the sphingosine. A parallel chain stacking is achieved by a sharp perpendicular bend of the fatty acid. This bend is produced by a sequence of two --60 degrees rotations about the C-C bonds at both sides of the alpha-carbon atom. The orientation of the hydrogen bond donors and acceptors of the amide group and the hydroxyl groups allow lateral interaction with other lipid molecules. The proposed models are supported by infrared spectra, thin-layer chromatographic behaviour and monolayer studies of synthetic model ceramides. The functional role of the hydrogen bonding groups in the ceramide part of sphingolipids is emphasized and their significance for the formation of lateral hydrogen bonds within the membrane layer and thereof arising effects on membrane stability and permeability are discussed.     

Solution NMR characterization of hydrogen bonds in a protein by indirect measurement of deuterium quadrupole couplings

Hydrogen bonds stabilize protein and nucleic acid structure, but little direct spectroscopic data have been available for characterizing these critical interactions in biological macromolecules. It is demonstrated that the electric field gradient at the nucleus of an amide hydrogen can be determined residue-specific by measurement of 15N NMR relaxation times in proteins dissolved in D2O, and uniformly enriched with 13C and 15N. In D2O, all backbone amide protons can be exchanged with solvent deuterons, and the T1 relaxation rate of a deuteron is dominated by its quadrupole coupling constant (QCC), which is directly proportional to the electric field gradient at the nucleus. 2HN T1 relaxation can be measured quantitatively through its effect on the T2 relaxation of its directly attached 15N. QCC values calculated from 2HN T1 and previously reported spectral densities correlate with the inverse cube of the X-ray crystal structure-derived hydrogen bond lengths: QCC = 228 + Sigmai 130 cos alphai/ri3 kHz, where alpha is the N-H...Oi angle and r is the backbone-backbone (N-)H...Oi(=C) hydrogen bond distance in angstroms.     

Alterations in follicular function associated with selection on ovulation rate in Finn ewes

A geometric docking algorithm based upon correlation analysis for quantification of geometric complementarity between protein molecular surfaces in close interfacial contact has been developed by a detailed optimization of the conformational search of the algorithm. In order to reduce the entire conformation space search required by the method a physico-chemical pre-filter of conformation space has been developed based upon the a priori assumption that two or more intermolecular hydrogen bonds are intrinsic to the mechanism of binding within protein complexes. Donor sites are defined spatially and directionally by the positions of explicitly calculated donor hydrogen atoms, and the vector space within a defined range about the donor atom-hydrogen atom bond vector. Acceptor sites are represented spatially and directionally by the van der Waals molecular surface points having normal vectors within a predefined range of vector space about the acceptor atom covalent bond vector(s). Geometric conditions necessary for the simultaneous hydrogen bonding interaction between both sites of functionally congruent hydrogen bonding site pairs, located on the individual proteins, are then tested on the basis of a transformation invariant parameterization of the site pair spatial and directional properties. Sterically acceptable conformations defined by interaction of functionally, spatially, and directionally compatible site pairs are then refined to a maximum contact of complementary contact surfaces using the simplex method for the angular search and correlation techniques for the translational search. The utility of the spatial and directional properties of hydrogen bonding donor and acceptor sites for the identification of candidate docking conformations is demonstrated by the reliable preliminary reduction of conformation space, the improved geometric ranking of the minimum RMS conformations of some complexes and the overall reduction of CPU time obtained.     

The binding of propranolol at 5-hydroxytryptamine1D beta T355N mutant receptors may involve formation of two hydrogen bonds to asparagine

Although the beta-adrenergic receptor antagonist (-)-propranolol binds with relatively low affinity at human 5-hydroxytryptamine1D beta receptors (Ki = 10,200 nM), it displays significantly higher affinity (Ki = 17 nM) at its species homolog, 5-HT1B receptors, and at a mutant 5-HT1D beta receptor (Ki = 16 nM), where the threonine residue at position 355 (T355) is replaced with an asparagine residue (i.e., a T355N mutant). Propranolol contains two oxygen atoms, an ether oxygen atom and a hydroxyl oxygen atom, and it has been speculated that the enhanced affinity of propranolol for the T355N mutant receptor is related to the ability of the asparagine residue to hydrogen bond with the ether oxygen atom. However, the specific involvement of the propranolol oxygen atoms in binding to the wild-type and T355N mutant 5-HT1D beta receptors has never been addressed experimentally. A modification of a previously described 5-HT1D beta receptor graphic model was mutated by replacement of T355 with asparagine. Propranolol was docked with the wild-type and T355N mutant 5-HT1D beta receptor models in an attempt to understand the difference in affinity of the ligand for the receptors. The binding models suggest that the asparagine residue of the mutant receptor can form hydrogen bonds with both oxygen atoms of propranolol, whereas the threonine moiety of the wild-type receptor can hydrogen-bond only to one oxygen atom. To test this hypothesis, we prepared and examined several analogues of propranolol that lacked either one or both oxygen atoms. The results of radioligand binding experiments are consistent with the hypothesis that both oxygen atoms of propranolol could participate in binding to the mutant receptor, whereas only the ether oxygen atom participates in binding to the wild-type receptor. As such, this is the first investigation of serotonin receptors that combines the use of molecular modeling, mutant receptors generated by site-directed mutagenesis, and synthesis to investigate structure/affinity relationships.     

The 0.78 A structure of a serine protease: Bacillus lentus subtilisin

Ultrahigh-resolution X-ray diffraction data from cryo-cooled, B. lentus subtilisin crystals has been collected to a resolution of 0.78 A. The refined model coordinates have a rms deviation of 0.22 A relative to the same structure determined at room temperature and 2.0 A resolution. Several regions of main-chain and side-chain disorder have been identified for 21 out of 269 residues in one polypeptide chain. Hydrogen atoms appear as significant peaks in the Fo - Fc difference electron density map, and carbon, nitrogen, and oxygen atoms can be differentiated. The estimated standard deviation (ESD) for all main-chain non-hydrogen bond lengths is 0.009 A and 0.5 degrees for bond angles based on an unrestrained full-matrix least-squares refinement. Hydrogen bonds are resolved in the serine protease catalytic triad (Ser-His-Asp). Electron density is observed for an unusual, short hydrogen bond between aspartic acid and histidine in the catalytic triad. The hydrogen atom, identified by NMR in numerous serine proteases, appears to be shared by the heteroatoms in the bond. This represents the first reported correlation between detailed chemical features identified by NMR and those in a cryo-cooled crystallographic structure determination at ultrahigh resolution. The short hydrogen bond, designated "catalytic hydrogen bond", occurs as part of an elaborate hydrogen bond network, involving Asp of the catalytic triad. While unusual, these features appear to have conserved analogues in other serine protease families although specific details differ from family to family.     

Computer simulation study on the conversion of spirolactone to enones over H-Y zeolite

We report here the results of computer modeling studies and quantum chemical calculations on the spirolactone-to-enone conversion reaction over the zeolite catalysts, especially H-Y zeolite. We studied the adsorption mode of the molecules inside the supercage of H-Y and the mechanism of electron transfer between organic molecules and the framework of zeolite H-Y by density functional theory (DFT) calculations. Because the organic molecules considered in the present study are less symmetrical we docked the molecule inside the supercage of H-Y and energy minimization was then applied to these docked structures to yield representative low-energy binding sites for the molecules within the host structure. The interaction energy results show that the major interaction is between the methylene hydrogen of the molecule and the oxygen of the framework. The molecular electrostatic potential maps show that the ketonic oxygen of the reactant molecules abstract proton from Br?nsted acid site. Thus the mechanism proposed by DFT calculation matches well with the experimental observations.     

两种新型希夫碱及其钴(Ⅱ)配合物的合成与表征

利用1-萘胺分别与邻香草醛和对甲氧基水杨醛反应合成两种新型希夫碱化合物L1和L2;用CoCl2.6H2O分别与L1和L2进行反应,获得了与其相对应两种新的配合物CoCl2L1(1)和CoCl2L22(2)。通过元素分析、红外光谱、1H-NMR及X射线粉末衍射等测试手段,对新型希夫碱及其配合物进行了表征。结果表明,两种希夫碱酚羟基上的H原子与N原子相吸均形成了分子内氢键,并以氢键连接构成了新的六元环。L1和L2作为配体与CoCl2形成配合物时,酚羟基上的H原子没有脱去。配合物1由L1和CoCl2以摩尔比1∶1组成,配体上酚羟基氧及甲氧基氧同时与中心原子Co配位,形成双齿螯合配位构型;配合物2由L2和CoCl2以摩尔比2∶1组成,配体上只有酚羟基氧参与中心原子Co的配位,而甲氧基氧未参与配位。配合物1,2中Co原子均为四配位的。     

Crystal Structure and Luminescence Spectra of Novel Coordination Layer of {[Eu(m-BDC)(NO3)(Phen)(H2O)]2·2CH3CH2OH}n

The crystal structure of a novel Eu3 coordination polymer, {[Eu(m-BDC)(NO3)(Phen)(H2O)]2 · 2CH3CH2OH}n (m-BDC=1,3-benzenedicarboxylate, Phen=1, 10-phenanthroline), was obtained and its high-resolution luminescence spectra at 77K were measured. The μ2-carboxylate of m-BDC constructs the binuclear building block in which each Eu3 ion is coordinated by four oxygen atoms of m-BDC anions, one oxygen atom from water molecule, two oxygen atoms of nitrate and two nitrogen atoms of Phen, respectively. The μ1-carboxylate of m-BDC conjugates the binuclear units one-dimensional chain or a ribbon, while the hydrogen bonds between ribbons assemble the structure two-dimensional layer with a thickness equaling to the width of the ribbon. The luminescence spectra reveal that the two Eu3 ion sites in the binuclear building blocks have slight environmental difference. The C1 local symmetry of Eu3 ion is concluded from both crystal structure measurement and luminescence spectra.     

The pre-Flexnerian reports: Mark Twain''s criticism of medicine in the United States

Dopamine has been implicated in the function of a diverse set of central nervous system and peripheral functions. We theoretically evaluated the chemistry of interaction between dopamine and its receptor using ab initio molecular orbital calculation. First, we calculated the total energy of dopamine on either a protonated or deprotonated molecule at the meta- or para-position hydroxy group of the catechol ring, and then evaluated the hydrogen bond effect in these hydroxy groups. These results suggested that the meta-position hydroxy group was liable to be protonated, and subsequently deprotonated by a negatively charged receptor site. It was considered that proton flopping, which occurred within the receptor site via the meta-position hydroxy group, appeared to be essential for exerting the biological action of dopamine. On the other hand, the para-position hydroxy group of the catechol ring contributed to stabilization of a dopamine molecule at the receptor site through a hydrogen bond. Second, we showed that the side-chain amino group of dopamine was readily protonated and bound a negatively charged receptor site by coulomb interaction. Third, we calculated the highest occupied molecular orbital and lowest unoccupied molecular orbital to elucidate chemical reactivities of these functional groups on the electron level. From the molecular orbital contour maps, it was suggested that frontier orbital interaction was involved in the dopamine-receptor interaction, in which the meta- and para-position hydroxy groups may function as a proton acceptor and a proton donor, respectively. Considering these theoretical results together, we hereby propose a model of the dopamine-receptor interaction: (1) a protonation-deprotonation at the meta-position hydroxy group takes place, (2) the protonated side-chain amino group of dopamine binds to a negatively charged receptor site by an ionic bond, and (3) the para-position hydroxy group not only contributes to stabilization for dopamine binding but may also enhance the protonation-deprotonation at the meta-position through bond interaction along the pi-bond between OH and the benzene ring.     

Structural behavior of F~- in mould flux melt of CaO-SiO_2-Al_2O_3-Na_2O-CaF_2 system

The influence of fluorine on the structure of CaO-SiO2-Al2O3-Na2O-CaF2 continuous-casting-type slag was measured by Raman spectroscopy, and the degree of polymerization of mould flux and the structural behavior of F- in the melt were investigated by classifying and quantifying the structural species of F- ions. The results exhibit that the main structural units of Si-O tetrahedra are Q0, Q1 and Q2, and the actual measured number of non-bridging oxygen ions in the ［SiO4］-tetrahedra (denoted by NBO/T) increases from 2.73 to 3.44 with increasing the molar ratio of F to (F+O) (denoted by XF/X(F+O)) from 0.06 to 0.19. It means that the degree of polymerization of melt structure decreases with an increase in XF/X(F+O). In addition, most of F- ions were distributed in Si-O tetrahedra and Al-O tetrahedra. With increasing XF/X(F+O), the complex structural units Al-O tetrahedra are gradually replaced by discrete structural units AlF4- because of the breakage of Al-O bonds in Al-O tetrahedra by F- ions, and the Si-O (bridging oxygen) bonds of Si-O tetrahedra are broken to form ［SiOnF4-n］-tetrahedra by F- ions coordinating with Si4+.     

Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding

Uracil phosphoribosyltransferase (UPRTase) catalyzes the transfer of a ribosyl phosphate group from alpha-D-5-phosphoribosyl-1-pyrophosphate to the N1 nitrogen of uracil. The UPRTase from the opportunistic pathogen Toxoplasma gondii is a rational target for antiparasitic drug design. To aid in structure-based drug design studies against toxoplasmosis, the crystal structures of the T.gondii apo UPRTase (1.93 A resolution), the UPRTase bound to its substrate, uracil (2.2 A resolution), its product, UMP (2.5 A resolution), and the prodrug, 5-fluorouracil (2.3 A resolution), have been determined. These structures reveal that UPRTase recognizes uracil through polypeptide backbone hydrogen bonds to the uracil exocyclic O2 and endocyclic N3 atoms and a backbone-water-exocyclic O4 oxygen hydrogen bond. This stereochemical arrangement and the architecture of the uracil-binding pocket reveal why cytosine and pyrimidines with exocyclic substituents at ring position 5 larger than fluorine, including thymine, cannot bind to the enzyme. Strikingly, the T. gondii UPRTase contains a 22 residue insertion within the conserved PRTase fold that forms an extended antiparallel beta-arm. Leu92, at the tip of this arm, functions to cap the active site of its dimer mate, thereby inhibiting the escape of the substrate-binding water molecule.     

Al-Er二元合金的价电子结构与固溶度研究

利用固体与分子经验电子理论(EET),计算分析了Al-Er合金的价电子结构。计算了不同温度下Er在基体铝中的平衡固溶度,同时结合界面前的溶质原子再分配原理,研究了在凝固过程中溶质原子Er的分配问题。结果表明:在Al3Er晶胞中最强Al-Er共价键的共价电子数为0.35798,表明Al-Er之间存在强烈的相互作用,在合金凝固过程中存在较大的形成金属间化合物Al3Er的趋势。固溶体中3种晶胞中最强键键能的关系为:EErEAl-ErEAl。因此Er元素的加入可以提高Al基体的结合强度,从而提高合金的抗高温性能。Er在基体铝中平衡固溶度很低,共晶温度928K下铒的固溶度仅为0.017%,平衡分配系数K约为0.00281,运用sheil模型计算表明当铒含量很低的情况下,凝固过程溶体中也会存在较大的成分过冷,随着凝固过程的进行,固液界面铒原子偏聚与铝结合生成Al3Er,起到异质形核的作用,细化了铸态晶粒组织。     

Metal-substrate interactions facilitate the catalytic activity of the bacterial phosphotriesterase

The bacterial phosphotriesterase from Pseudomonas diminuta is a zinc metalloenzyme which catalyzes the hydrolysis of a variety of organophosphorus nerve agents with high efficiency. The active site of the enzyme consists of a coupled binuclear metal center embedded within a cluster of histidine residues. Potential protein-substrate interactions at the active site were probed by a systematic variation of metal identity, leaving group potential, phosphate host, and amino acid replacement. In order to determine the roles of these metal ions in binding and catalysis, the microscopic rate constants and kinetic parameters were obtained with various divalent cations. The divalent cations that were utilized in this investigation consisted of Co2+, Ni2+, Cd2+, Zn2+, Mn2+, and the mixed-metal Zn2+/Cd2+ hybrid. The leaving group potential and phosphate host were varied by altering the pKa of the departing substituted phenol or thiophenol in either a diethyl phosphate or a diethyl thiophosphate substrate. The Br?nsted plots for the nonenzymatic hydroxide catalyzed hydrolysis of these substrates showed a linear dependence between the pseudo-first-order rate constant and the pKa of the leaving group. Enzymatic activities of the wild-type enzyme with these same substrates varied by over 7 orders of magnitude over the entire experimental pKa range (4.1-10.3), and the corresponding Br?nsted plots were nonlinear. Those substrates with leaving groups with high pKa values were limited by the rate of bond cleavage while those substrates having leaving groups with low pKa values were limited by a conformational change or binding event. Thiophosphate substrates having leaving groups with high pKa values were better substrates than the corresponding phosphate analogues. These results are consistent with the direct coordination of one or both metal ions with the phosphoryl sulfur or oxygen atom of the substrate. A large dependence of the rate on the leaving group rules out the possibility of protonation of the leaving group or electrostatic interaction of the leaving group oxygen (or sulfur) with a metal ion or cationic group at the active site. The large differences in the size of the beta lg over the range of metal ions utilized by the enzyme indicate that the metal ions polarize the phosphoryl group and alter the structure of the transition state. The values of V/K(m) for the enzyme-catalyzed hydrolysis for a series of substituted thiophenol analogues were 10(2)-10(3)-fold smaller than those obtained for the hydrolysis of the corresponding phenolic substrates, suggesting that the bulkier sulfur substituent in the leaving group may induce conformational restrictions at the active site. With the zinc-substituted H201N mutant enzyme, there was a large decrease in the rate of phosphotriester hydrolysis but essentially no change in the rate of thiophosphotriester hydrolysis relative to the values observed for the zinc-substituted wild-type enzyme. These results suggest that a direct perturbation in the ligand structure of the binuclear metal center induces alterations in the mechanism of substrate hydrolysis.     

酒钢SPCC钢的LF精炼脱硫

 通过热力学分析,建立了硫分配比与硫容量的关系,用热力学软件FactSage计算渣中Al2O3活度,用KTH模型计算渣的硫容量,对SPCC(一般用冷轧碳素钢薄板坯钢带)两个浇次10炉钢水在LF进站和出站时取钢、渣样以及测氧和温度,通过分析钢样和渣样成分以及生产检测数据,分析了温度、炉渣成分和钢水成分对LF精炼脱硫的影响规律。定义了硫分配比对钢液中溶解氧活度的急剧变化区(a［O］＜4×10-6),在该区内硫分配比对钢液中溶解氧活度十分敏感,钢液中氧活度的增大导致硫分配比的迅速减小,温度升高,a［O］升高,不仅抵消了升温对脱硫反应轻微的促进作用,反而使硫分配比随温度升高而减小。LF精炼过程Al-O反应未达渣-钢平衡,实际［O］活度介于平衡计算值与Al2O3活度为1的计算值之间,故渣钢硫分配比也介于二者之间。精炼渣二元碱度升高则硫分配比增加,wCaO/wAl2O3在1.6~2.0时脱硫效果较好,硫分配比并不随［Al］s含量的增加而增大,所以用增加w［Al］s来脱硫效果并不明显。钢中夹杂铝(w［Al］t-w［Al］s)降低到10×10-6以下,硫分配比明显升高。     

Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants

The contribution of hydrogen bonds to the conformational stability of human lysozyme was investigated by the combination of calorimetric and X-ray analyses of six Tyr --> Phe mutants. Unfolding Delta G and unfolding Delta H values of the Tyr --> Phe mutant proteins were changed by from +0.3 to -4.0 kJ/mol and from 0 to -16 kJ/mol, respectively, compared to those of the wild-type protein. The net contribution of a hydrogen bond at a specific site to stability (Delta Gwild/HB), considering factors affected by substitutions, was evaluated on the basis of X-ray structures of the mutant proteins. In the present study, one of six mutant proteins was suitable for evaluating the strength of the hydrogen bond. Delta Gwild/HB for the intramolecular hydrogen bond at Tyr124 was evaluated to be 7.5 kJ/mol. Results of the analysis of other mutants also suggest that hydrogen bonds of the hydroxyl group of Tyr, including the hydrogen bond with a water molecule, contribute to the stabilization of the human lysozyme.     

Mechanism of enolase: the crystal structure of asymmetric dimer enolase-2-phospho-D-glycerate/enolase-phosphoenolpyruvate at 2.0 A resolution

Enolase, a glycolytic enzyme that catalyzes the dehydration of 2-phospho-d-glycerate (PGA) to form phosphoenolpyruvate (PEP), is a homodimer in all eukaryotes and many prokaryotes. Here, we report the crystal structure of a complex between yeast enolase and an equilibrium mixture of PGA and PEP. The structure has been refined using 29 854 reflections with an F/sigma(F) of >/=3 to an R of 0.137 with average deviations of bond lengths and bond angles from ideal values of 0.013 A and 3.1 degrees , respectively. In this structure, the dimer constitutes the crystallographic asymmetric unit. The two subunits are similar, and their superposition gives a rms distance between Calpha atoms of 0.91 A. The exceptions to this are the catalytic loop Val153-Phe169 where the atomic positions in the two subunits differ by up to 4 A and the loop Ser250-Gln277, which follows the catalytic loop Val153-Phe169. In the first subunit, the imidazole side chain of His159 is in contact with the phosphate group of the substrate/product molecule; in the other it is separated by water molecules. A series of hydrogen bonds leading to a neighboring enolase dimer can be identified as being responsible for ordering and stabilization of the conformationally different subunits in the crystal lattice. The electron density present in the active site suggests that in the active site with the direct ligand-His159 hydrogen bond PGA is predominantly bound while in the active site where water molecules separate His159 from the ligand the binding of PEP dominates. The structure indicates that the water molecule hydrating carbon-3 of PEP in the PEP --> PGA reaction is activated by the carboxylates of Glu168 and Glu211. The crystals are unique because they have resolved two intermediates on the opposite sides of the transition state.     

Crystal structures of the inactive D30N mutant of feline immunodeficiency virus protease complexed with a substrate and an inhibitor

Crystal structures of complexes of a D30N mutant of feline immunodeficiency virus protease (FIV PR) complexed with a statine-based inhibitor (LP-149), as well as with a substrate based on a modification of this inhibitor (LP-149S), have been solved and refined at resolutions of 2.0 and 1.85 A, respectively. Both the inhibitor and the substrate are bound in the active site of the mutant protease in a similar mode, which also resembles the mode of binding of LP-149 to the native protease. The carbonyl oxygen of the scissile bond in the substrate is not hydrated and is located within the distance of a hydrogen bond to an amido nitrogen atom from one of the two asparagines in the active site of the enzyme. The nitrogen atom of the scissile bond is 3.25 A from the conserved water molecule (Wat301). A model of a tetrahedral intermediate bound to the active site of the native enzyme was built by considering the interactions observed in all three crystal structures of FIV PR. Molecular dynamics simulations of this model bound to native wild-type FIV PR were carried out, to investigate the final stages of the catalytic mechanism of aspartic proteases.     

Prediction of activities of oxygen in dilute quaternary solutions using binary data

Equations are developed for predicting the activity coefficients of oxygen dissolved in ternary liquid alloys. These are extensions of earlier treatments, and are based on a model in which each oxygen atom is assumed to make four bonds with neighboring metal atoms. It is also postulated that the strong oxygen-metal bonds distort the electronic configuration around the metal atoms bonded to oxygen, and that the quantitative reduction of the strength of bonds made by these atoms with all of the adjacent metal atoms is equivalent to a factor of approximately two. The predictions of the quasichemical equation which is derived agree satisfactorily with the partial molar free energies of oxygen in Ag-Cu-Sn solutions at 1200°C reported in literature. An extension of this treatment to multicomponent solutions is also indicated.