The application of inverse Broyden’s algorithm for modeling of crack growth in iron crystals

In the present paper we demonstrate the use of inverse Broyden’s algorithm (IBA) in the simulation of fracture in single iron crystals. The iron crystal structure is treated as a truss system, while the forces between the atoms situated at the nodes are defined by modified Morse inter-atomic potentials. The evolution of lattice structure is interpreted as a sequence of equilibrium states corresponding to the history of applied load/deformation, where each equilibrium state is found using an iterative procedure based on IBA. The results presented demonstrate the success of applying the IBA technique for modeling the mechanisms of elastic, plastic and fracture behavior of single iron crystals.     

Strong and weak hydrogen bonds in drug-DNA complexes: A statistical analysis

A statistical analysis of strong and weak hydrogen bonds in the minor groove of DNA was carried out for a set of 70 drug-DNA complexes. The terms ‘strong’ and ‘weak’ pertain to the inherent strengths and weakness of the donor and acceptor fragments rather than to any energy considerations. The dataset was extracted from the protein data bank (PDB). The analysis was performed with an in-house software, hydrogen bond analysis tool (HBAT). In addition to strong hydrogen bonds such as O—H⋯O and N—H⋯O, the ubiquitous presence of weak hydrogen bonds such as C—H⋯O is implicated in molecular recognition. On an average, there are 1.4 weak hydrogen bonds for every strong hydrogen bond. For both categories of interaction, the N(3) of purine and the O(2) of pyrimidine are favoured acceptors. Donor multifurcation is common with the donors generally present in the drug molecules, and shared by hydrogen bond acceptors in the minor groove. Bifurcation and trifurcation are most commonly observed. The metrics for strong hydrogen bonds are consistent with established trends. The geometries are variable for weak hydrogen bonds. A database of recognition geometries for 26 literature amidinium-based inhibitors of Human African Trypanosomes (HAT) was generated with a docking study using seven inhibitors which occur in published crystal structures included in the list of 70 complexes mentioned above, and 19 inhibitors for which the drug-DNA complex crystal structures are unknown. The virtual geometries so generated correlate well with published activities for these 26 inhibitors, justifying our assumption that strong and weak hydrogen bonds are optimized in the active site.     

Vibrational frequency shifts as a probe of hydrogen bonds: thermal expansion and glass transition of myoglobin in mixed solvents

The contribution of hydrogen bonds to protein-solvent interactions and their impact on structural flexibility and dynamics of myoglobin are discussed. The shift of vibrational peak frequencies with the temperature of myoglobin in sucrose/water and glycerol/water solutions is used to probe the expansion of the hydrogen bond network. We observe a characteristic change in the temperature slope of the O–H stretching frequency at the glass transition which correlates with the discontinuity of the thermal expansion coefficient. The temperature-difference spectra of the amide bands show the same tendency, indicating that stronger hydrogen bonding in the bulk affects the main-chain solvent interactions in parallel. However, the hydrogen bond strength decreases relative to the bulk solvent with increasing cosolvent concentration near the protein surface, which suggests preferential hydration. Weaker and/or fewer hydrogen bonds are observed at low degrees of hydration. The central O–H stretching frequency of protein hydration water is red-shifted by 40 cm^–1 relative to the bulk. The shift increases towards lower temperatures, consistent with contraction and increasing strength of the protein-water bonds. The temperature slope shows a discontinuity near 180 K. The contraction of the network has reached a critical limit which leads to frozen-in structures. This effect may represent the molecular mechanism underlying the dynamic transition observed for the mean square displacements of the protein atoms and the heme iron of myoglobin. Received: 10 July 1996 / Accepted: 10 April 1997     

The Alkaline Solution to the Emergence of Life: Energy,Entropy and Early Evolution

The Earth agglomerates and heats. Convection cells within the planetary interior expedite the cooling process. Volcanoes evolve steam, carbon dioxide, sulfur dioxide and pyrophosphate. An acidulous Hadean ocean condenses from the carbon dioxide atmosphere. Dusts and stratospheric sulfurous smogs absorb a proportion of the Sun’s rays. The cooled ocean leaks into the stressed crust and also convects. High temperature acid springs, coupled to magmatic plumes and spreading centers, emit iron, manganese, zinc, cobalt and nickel ions to the ocean. Away from the spreading centers cooler alkaline spring waters emanate from the ocean floor. These bear hydrogen, formate, ammonia, hydrosulfide and minor methane thiol. The thermal potential begins to be dissipated but the chemical potential is dammed. The exhaling alkaline solutions are frustrated in their further attempt to mix thoroughly with their oceanic source by the spontaneous precipitation of biomorphic barriers of colloidal iron compounds and other minerals. It is here we surmise that organic molecules are synthesized, filtered, concentrated and adsorbed, while acetate and methane—separate products of the precursor to the reductive acetyl-coenzyme-A pathway—are exhaled as waste. Reactions in mineral compartments produce acetate, amino acids, and the components of nucleosides. Short peptides, condensed from the simple amino acids, sequester ‘ready-made’ iron sulfide clusters to form protoferredoxins, and also bind phosphates. Nucleotides are assembled from amino acids, simple phosphates carbon dioxide and ribose phosphate upon nanocrystalline mineral surfaces. The side chains of particular amino acids register to fitting nucleotide triplet clefts. Keyed in, the amino acids are polymerized, through acid–base catalysis, to alpha chains. Peptides, the tenuous outer-most filaments of the nanocrysts, continually peel away from bound RNA. The polymers are concentrated at cooler regions of the mineral compartments through thermophoresis. RNA is reproduced through a convective polymerase chain reaction operating between 40 and 100°C. The coded peptides produce true ferredoxins, the ubiquitous proteins with the longest evolutionary pedigree. They take over the role of catalyst and electron transfer agent from the iron sulfides. Other iron–nickel sulfide clusters, sequestered now by cysteine residues as CO-dehydrogenase and acetyl-coenzyme-A synthase, promote further chemosynthesis and support the hatchery—the electrochemical reactor—from which they sprang. Reactions and interactions fall into step as further pathways are negotiated. This hydrothermal circuitry offers a continuous supply of material and chemical energy, as well as electricity and proticity at a potential appropriate for the onset of life in the dark, a rapidly emerging kinetic structure born to persist, evolve and generate entropy while the sun shines. An erratum to this article can be found at     

A theoretical study of red-shifting and blue-shifting hydrogen bonds occurring between imidazolidine derivatives and PEG/PVP polymers

A theoretical study is presented with the aim to investigate the molecular properties of intermolecular complexes formed by the monomeric units of polyvinylpyrrolidone (PVP) or polyethyleneglycol (PEG) polymers and a set of four imidazolidine (hydantoine) derivatives. The substitution of the carbonyl groups for thiocarbonyl in the hydantoin scaffold was taken into account when analyzing the effect of the hydrogen bonds on imidazolidine derivatives. B3LYP/6-31G(d,p) calculations and topological integrations derived from the quantum theory of atoms in molecules (QTAIM) were applied with the purpose of examining the N–H⋯O hydrogen bond strengths formed between the amide group of the hydantoine ring and the oxygen atoms of PVP and PEG polymers. The effects caused by the N–H⋯O interaction fit the typical evidence for hydrogen bonds, which includes a variation in the stretch frequencies of the N–H bonds. These frequencies were identified as being vibrational red-shifts because their values decreased. Although the values of such calculated interaction energies are between 12 and 33 kJ mol⁻¹, secondary intermolecular interactions were also identified. One of these secondary interactions is formed through the interaction of the benzyl hydrogen atoms with the oxygen atoms of the PVP and PEG structures. As such, we have analyzed the stretch frequencies on the C–H bonds of the benzyl groups, and blue-shifts were identified on these bonds. In this sense, the intermolecular systems formed by hydantoine derivatives and PVP/PEG monomers were characterized as a mix of red-shifting and blue-shifting hydrogen-bonded complexes.     

Hydrogeomorphic Controls on Reduction–Oxidation Conditions across Boreal Upland–Peatland Interfaces

The reduction–oxidation (redox) state of peatland pore waters plays an important role in many peatland biogeochemical processes. Recent research has also shown that the interface between ecosystems, or the ecotone, may be responsible for a disproportionate amount of biogeochemical activity when material and/or energy is hydrologically transported between ecosystems. The purpose of this research was to examine the spatiotemporal dynamics of redox conditions across two geomorphically distinct Boreal Precambrian Shield upland–peatland ecotones to determine the spatial and temporal scales at which these ecotones may be important. Pore water chemistry of iron and sulphur species was monitored across two upland–peatland ecotones in northwestern Ontario in conjunction with hydrological measurements under both stormflow and nonstormflow conditions. In addition, one upland–peatland ecotone was instrumented to make continuous measurements of in situ redox potential (Eh) over a 12-day period to determine whether measurements at a high temporal scale could provide additional insights into the transfer of nutrients across the upland–peatland interface. Results indicated that hydrology—specifically, groundwater flowpath and the strength of the hydrological connection between upland and peatland—determined the spatial extent of the ecotone as a biogeochemical hotspot. In situ Eh measurements showed that these ecotones may be most important over a scale of only several hours and are largely affected by lateral hydrological flows from the upland. The role of both hot spots and hot moments in biogeochemistry must be considered to accurately estimate the ability of a single ecosystem to process chemical inputs.     

Maternal Milk Concentration of Zinc,Iron, Selenium,and Iodine and Its Relationship to Dietary Intakes

The dietary intake of zinc (Zn), iron (Fe), selenium (Se), and iodine (I) of 31 lactating Mexican–American women attending the Hidalgo County WIC program in Rio Grande Valley (RGV), Texas was estimated from 24-h dietary recall interviews. Milk samples were obtained from lactating mothers who had infants 3 months of age and younger. Milk samples were collected in two visits to assess change in breast milk composition after 1–3 months postpartum: group A—after 30–45 days and group B—75–90 days. Dietary intakes indicated that the study participants had significantly inadequate percent energy intakes than the DRI (Dietary Recommended Intakes) percent recommended kilocalorie values but protein intakes were substantially higher than the percent recommended values. The estimated percent Zn, Fe, Se, and I intakes were also significantly lower than the DRI percent recommended values. The lactating mothers consumed significantly less Zn, Se, and I when compared to the Recommended Dietary Allowances (RDA) even though Fe intake was higher than the RDA value. Breast milk concentration of Zn, Fe, and Se were in agreement within the range of representative values for Constituents of Human Milk but I has significantly less concentration than the representative value. There was no statistically significant correlation observed between dietary intake and milk concentration of Zn, Fe, Se, and I. This study compares the estimated dietary intake of zinc, iron, selenium, and iodine to the concentration of these trace elements in the maternal milk of lactating women of Mexican–American heritage who attend the Rio Grande Valley WIC clinic.     

Mobilization of storage iron is reflected in the iron isotopic composition of blood in humans

We recently showed in an animal model that iron isotopic composition varies substantially between different organs. For instance, iron in ferritin-rich organs—such as the major storage tissues liver, spleen, and bone marrow—contain a larger fraction of the heavy iron isotopes compared with other tissues, including blood. As a consequence, partitioning of body iron into red blood cells and storage compartments should be reflected in the isotopic pattern of blood iron. To confirm this hypothesis, we monitored blood iron isotope patterns in iron-overloaded subjects undergoing phlebotomy treatment by multicollector inductively coupled plasma mass spectrometry. We found that bloodletting and consequential replacement of lost blood iron by storage iron led to a substantial increase of the heavy isotope fraction in the blood. The progress of iron depletion therapy and blood loss was quantitatively traceable by isotopic shifts of as much as +1‰ in δ(⁵⁶Fe). These results show that—together with iron absorption efficiency—partitioning of iron between blood and iron storage tissues is an important determinant of blood iron isotopic patterns, which could make blood iron isotopic composition the first composite measure of iron metabolism in humans.     

Noscapinoids with anti-cancer activity against human acute lymphoblastic leukemia cells (CEM): a three dimensional chemical space pharmacophore modeling and electronic feature analysis

We have identified a new class of microtubule-binding compounds—noscapinoids—that alter microtubule dynamics at stoichiometric concentrations without affecting tubulin polymer mass. Noscapinoids show great promise as chemotherapeutic agents for the treatment of human cancers. To investigate the structural determinants of noscapinoids responsible for anti-cancer activity, we tested 36 structurally diverse noscapinoids in human acute lymphoblastic leukemia cells (CEM). The IC₅₀ values of these noscapinoids vary from 1.2 to 56.0 μM. Pharmacophore models of anti-cancer activity were generated that identify two hydrogen bond acceptors, two aromatic rings, two hydrophobic groups, and one positively charged group as essential structural features. Additionally, an atom-based quantitative structure–activity relationship (QSAR) model was developed that gave a statistically satisfying result (R ² = 0.912, Q ² = 0.908, Pearson R = 0.951) and effectively predicts the anti-cancer activity of training and test set compounds. The pharmacophore model presented here is well supported by electronic property analysis using density functional theory at B3LYP/3-21*G level. Molecular electrostatic potential, particularly localization of negative potential near oxygen atoms of the dimethoxy isobenzofuranone ring of active compounds, matched the hydrogen bond acceptor feature of the generated pharmacophore. Our results further reveal that all active compounds have smaller lowest unoccupied molecular orbital (LUMO) energies concentrated over the dimethoxy isobenzofuranone ring, azido group, and nitro group, which is indicative of the electron acceptor capacity of the compounds. Results obtained from this study will be useful in the efficient design and development of more active noscapinoids.     

Balance of CO molecules in the plasma of a sealed-off CO laser

Abstrac The processes of dissociation and recombination of CO molecules in the plasmas of discharges in He/CO and He/CO/Xe mixtures under conditions characteristic of sealed-off CO lasers are investigated. The concentrations of CO molecules and the main products of their dissociation—O and C atoms and CO₂ molecules—are measured simultaneously for the first time, and the time evolution of the initial working mixture composition in the discharge is calculated. It is shown that the main channel for the regeneration of CO molecules in a sealed-off discharge is the heterogeneous recombination of C and O atoms. The rate constants for this process are estimated. __________ Translated from Fizika Plazmy, Vol. 30, No. 9, 2004, pp. 845–854. Original Russian Text Copyright ? 2004 by Grigorian, Kochetov.     

Simple menaquinones reduce carbon tetrachloride and iron (III)

Cell-free supernatant from Shewanella oneidensis MR-1 reduced carbon tetrachloride to chloroform, a suspension of Fe(III) and solid Fe(III) to iron (II). The putative reducing agent was tentatively identified as menaquinone-1 (MQ-1)—a water-soluble menaquinone with a single isoprenoid residue in the side chain. Synthetic MQ-1 reduced carbon tetrachloride to chloroform and amorphous iron (III) hydroxide to iron (II). To test the generality of this result among menaquinones, the reductive activities of vitamin K₂ (MQ-7)—a lipid-associated menaquinone with 7 or 8 isoprenoid residues—was evaluated. This molecule also reduced carbon tetrachloride to chloroform and iron (III) to iron (II). The results indicate that molecules within the menaquinone family may contribute to both the extracellular and cell-associated reduction of carbon tetrachloride and iron (III).     

Visualization of Reinke’s crystals in normal and cryptorchid testis

Within the human testis, Reinke’s crystals are found in Leydig cells but their nature and function are poorly understood. The aim of our study was to investigate the properties of Reinke’s crystals in man with the normal morphology of the testis (control group) and infertile patients diagnosed with cryptorchidism. 20 biopsies from infertile patients and six biopsies from men with regular spermatogenesis (20–30 years.) were used. Sections of the testis tissue were stained with haematoxylin and eosin and a modified Masson’s method. Specimens were observed by bright field, confocal and transmission electron microscopy (TEM). The number of Reinke’s crystals in investigated groups was determined applying stereological methods. In both groups, Reinke’s crystals were noted within the cytoplasm and nuclei of Leydig cells. Some “free” crystals were found within the interstitial space, outside Leydig cells. Confocal microscopy proved to be very useful in the assessment of the shape and 3D reconstruction of the crystal. TEM analysis confirmed a hexagonal form of the crystal, while crystallographic data on sections of 70–300 nm thickness provided a better insight into the organization of the crystal lattice. Stereological analysis revealed a significant increase in the number of crystals in cryptorchid testes when compared with controls. Increased number of crystals in cryptorchid specimens leads to the assumption that the prolonged exposure to higher (abdominal) temperature might stimulate enzymes involved in the synthesis of the proteins of the crystal. However, the exact molecular nature of the crystal lattice remains in both normal and cryptorchid testis obscure.     

Computer simulation of polypeptides in a confinement

A coarse-grained model of polypeptide chains confined in a slit formed by two parallel impenetrable surfaces was studied. The chains were flexible heteropolymers (polypeptides) built of two kinds of united atoms—hydrophobic and hydrophilic. The positions of the united atoms were restricted to the vertices of a [310] lattice. The force field consisted of a rigorous excluded volume, a long-distance potential between a pair of amino-acid residues and a local preference for forming secondary structure (helices). The properties of the chains were studied at a wide range of temperatures from good to bad solvent conditions. Monte-Carlo simulations were carried out using the algorithm based on the chain’s local changes of conformation and employing the Replica Exchange technique. The influence of the chain length, the distances between the confining surfaces, the temperature and the force field on the dimension and the structure of chains were studied. It was shown that the presence of the confinement chain complicates the process of the chain collapse to low-temperature structures. For some conditions, one can find a rapid decrease of chain size and a second transition indicated by the rapid decrease of the total energy of the system. Figure A scheme of a polypeptide chain built on a [310] lattice and confined to a slit formed by a pair of parallel impenetrable surfaces Proceedings of “Modeling Interactions in Biomolecules II,” Prague, September 5th–9th, 2005.     

A Review of the Antioxidant Mechanisms of Polyphenol Compounds Related to Iron Binding

In this review, primary attention is given to the antioxidant (and prooxidant) activity of polyphenols arising from their interactions with iron both in vitro and in vivo. In addition, an overview of oxidative stress and the Fenton reaction is provided, as well as a discussion of the chemistry of iron binding by catecholate, gallate, and semiquinone ligands along with their stability constants, UV–vis spectra, stoichiometries in solution as a function of pH, rates of iron oxidation by O₂ upon polyphenol binding, and the published crystal structures for iron–polyphenol complexes. Radical scavenging mechanisms of polyphenols unrelated to iron binding, their interactions with copper, and the prooxidant activity of iron–polyphenol complexes are briefly discussed.     

Influence of point defects on the electronic properties of boron nitride nanosheets

Density functional theory was utilized to study the electronic properties of boron nitride (BN) sheets, taking into account the presence of defects. The structure considered consisted of a central hexagon surrounded by alternating pentagons (three) and heptagons (three). The isocoronene cluster model with an armchair edge was used with three different chemical compositions. In the first structure, three B–B bonds were formed where one B in the dimer was part of the central hexagon. In the second structure, three N–N–N bonds were formed at the periphery of the cluster, around the central hexagon. In the third structure, three N–N bonds were formed in a similar fashion to the first model. Our results indicated that the third structure was the most stable configuration; this exhibited planar geometry, semiconductor behavior, and ionic character. To explore the effects of doping, we replaced B and N atoms with C atoms, considering different atomic positions in the central hexagon. When an N atom was replaced with a C atom, the new structure was a semiconductor, but when a B atom was replaced with a C atom, the new structure was a semimetal. At the same time, the polarity increased, inducing covalent behavior. Replacing two N atoms with two C atoms also resulted in a semiconductor, while replacing two B atoms with two C atoms yielded a semimetal; in both cases the bonding was covalent. When three B (three N) atoms of the central hexagon were replaced with three C atoms, the new structure exhibited a transition to a conductor (remained a semiconductor) with low polarity. When monovacancies (N) and divacancies (B and N) were inserted into the lattice, the system was transformed into a covalent semiconductor. Finally, the electrostatic potential surface was calculated in order to explore intermolecular properties such as the charge distribution, which showed how the reactivity of the boron nitride sheets was affected by doping and orbital hybridization.     

The concentration of twelve elements in the anterior pituitary from human subjects and rats as measured by particle induced X-ray emission (PIXE)

The concentration of twelve elements—potassium, calcium, manganese, iron, cobalt, nickel, copper, zinc, arsenic, selenium, bromine, and rubidium—in anterior pituitaries from human subjects and rats was measured using Particle Induced X-ray Emission (PIXE). The human material included anterior pituitaries from 37 normal human subjects, 27 males and 10 females, all of whom died from traumatic lesions. Excluded from the investigations were persons with alcohol abuse, regular use of drugs, and babies younger than 1 year. For selenium, zinc, bromine, and to some extent copper, there was good correlation between the amounts found in anterior pituitaries from rats and human subjects. A significant difference between male and female rat pituitaries was observed for copper, iron, and rubidium, whereas for humans significant difference was only observed for manganese. Anterior pituitaries from human females contained generally more zinc than male glands, but the concentration of zinc in young males was higher than in females. The present study also indicates age related differences in the copper content in anterior pituitaries from human subjects, since pituitaries from humans between 15–45 years contained 25% more copper than those from younger or older persons. The opposite pattern was observed in males. For such elements as Cu, Fe, Mn, and Se, the content in the anterior pituitary from human subjects was 1.6–2 times that stated for other endocrine organs.     

Ontogenesis of the cricket Gryllus argentinus Sauss. (Orthoptera, Gryllidae)

The development of Gryllus argentinus Sauss. was studied under stable laboratory conditions: the temperature of 26°C, the air humidity of 60%, and the photoperiod of 12h light: 12 h dark. The life cycle of Gryllus argentinus includes four stages: egg, pronymph, nymph, and adult. The duration of embryonic development is 18 days. The depth of egg bedding in the peat is 9.63 ± 0.12 mm (n =145), the clutch containing 2–4 eggs. A female can lay over 1100 viable eggs during the entire oviposition period. Nymphal development includes 9 instars and lasts 97 days. The duration of nymphal instars (days) is: I—5; II—6; III—6; IV—6; V—8; VI—10; VII—13; VIII—14; IX—29. The duration of the adult life is 51 days in males and 69 days, in females. In the imaginal ontogenesis of males and females, three periods can be distinguished: pre-reproductive, reproductive, and postreproductive. Males start to emit the aggressive signal on the 6th (5–8th) day (the pre-reproductive period). They enter the reproductive period (start to emit the calling song) on the 9th (8–13th) day. Females enter the reproductive period (become capable of responding to the calling song and of copulation) on the 9th (8–10th) day. Oviposition starts on the day after the first copulation. The reproductive period lasts about 40 (15–59) days in males and 58 (21–70) days in females. The post-reproductive period starts in females at the moment of finishing the egg laying period and in males, with disappearance of reproductive behavior. The period ends in the animal’s death.     

Crystal structure and conformational analysis of s-cis-(acetylacetonato)(ethylenediamine-N,N′-diacetato)-chromium(III)

The crystal structure of [Cr(edda)(acac)] (edda = ethylediamine-N,N′-diacetate; acac = acetylacetonato) has been determined by a single crystal X-ray diffraction study at 150 K. The chromium ion is in a distorted octahedral environment coordinated by two N and two O atoms of chelating edda and two O atoms of acac, resulting in s-cis configuration. The complex crystallizes in the space group P2₁/c of the monoclinic system in a cell of dimensions a = 10.2588(9), b = 15.801(3), c = 8.7015(11) ?, β =101.201(9)° and Z = 4. The mean Cr-N(edda), Cr-O(edda) and Cr-O(acac) bond distances are 2.0829(14), 1.9678(11) and 1.9477(11) ? while the angles O-Cr-O of edda and O-Cr-O of acac are 171.47(5) and 92.72(5)°, respectively. The crystal structure is stabilized by N–H⋯O hydrogen bonds linking [Cr(edda)(acac)] molecules in distinct linear strands. The visible electronic and IR spectroscopic properties are also discussed. An improved, physically more realistic force field, Vibrationally Optimized Force Field (VOFF), capable of reproducing structural and vibrational properties of [Cr(edda)(acac)] was developed and its transferability demonstrated on selected chromium(III) complexes with similar ligands.     

Chitosan antiviral activity: Dependence on structure and depolymerization method

Enzymatic (the action of lysozyme) and chemical (the action of hydrogen peroxide) hydrolysis of chitosans with various degree of acetylation (DA)—25, 17, and 1.5%—was performed. Purification and fractioning of the hydrolysis products were performed using dialysis, ultrafiltration, and gel-penetrating chromatography. Low-molecular (LM) derivatives of the polysaccharide with molecular masses from 17 to 2 kDa were obtained. The study of their antiviral activity against the tobacco mosaic virus (TMV) showed that these samples inhibited the formation of local necroses induced by the virus for 50–90%. The antiviral activity of the LM chitosans significantly increased with the lowering of their polymerization degree. Furthermore, the products of the enzymatic hydrolysis possessed lower activity than the chitosan samples obtained as a result of chemical hydrolysis. It was revealed that the exhibition of the antiviral activity weakly depended on the degree of acetylation of the samples.     

Analysis of structural water and CH···π interactions in HIV-1 protease and PTP1B complexes using a hydrogen bond prediction tool,HBPredicT

A hydrogen bond prediction tool HBPredicT is developed for detecting structural water molecules and CH···π interactions in PDB files of protein-ligand complexes. The program adds the missing hydrogen atoms to the protein, ligands, and oxygen atoms of water molecules and subsequently all the hydrogen bonds in the complex are located using specific geometrical criteria. Hydrogen bonds are classified into various types based on (i) donor and acceptor atoms, and interactions such as (ii) protein-protein, (iii) protein-ligand, (iv) protein-water, (v) ligand-water, (vi) water-water, and (vii) protein-water-ligand. Using the information in category (vii), the water molecules which form hydrogen bonds with the ligand and the protein simultaneously–the structural water–is identified and retrieved along with the associated ligand and protein residues. For CH···π interactions, the relevant portions of the corresponding structures are also extracted in the output. The application potential of this program is tested using 19 HIV-1 protease and 11 PTP1B inhibitor complexes. All the systems showed presence of structural water molecules and in several cases, the CH···π interaction between ligand and protein are detected. A rare occurrence of CH···π interactions emanating from both faces of a phenyl ring of the inhibitor is identified in HIV-1 protease 1D4L.