bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the N‐terminal half‐saturated state of calbindin D9k: NMR studies of the N56A mutant
Authors: Wimberly Brian , Chazin Walter J. , Thulin Eva 
Published: June 2010

AbstractCalbindin D9k is a small EF‐hand protein that binds two calcium ions with positive cooperativity. The molecular basis of cooperativity for the binding pathway where the first ion binds in the N‐terminal site (I) is investigated by NMR experiments on the half‐saturated state of the N56A mutant, which exhibits sequential yet cooperative binding (Linse S, Chazin WJ, 1995, Protein Sci 4:1038–1044). Analysis of calcium‐induced changes in chemical shifts, amide proton exchange rates, and NOEs indicates that ion binding to the N‐terminal binding loop causes significant changes in conformation and/or dynamics throughout the protein. In particular, all three parameters indicate that the hydrophobic core undergoes a change in packing to a conformation very similar to the calcium‐loaded state. These results are similar to those observed for the (Cd2+)1 state of the wild‐type protein, a model for the complementary half‐saturated state with an ion bound in the C‐terminal site (II). Thus, with respect to cooperativity in either of the binding pathways, binding of the first ion drives the conformation and dynamics of the protein far toward the (Ca2+)2 state, thereby facilitating binding of the second ion. Comparison with the half‐saturated state of the analogous E65Q mutant confirms that mutation of this critical bidentate calcium ligand at position 12 of the consensus EF‐hand binding loop causes very significant structural perturbations. This result has important implications regarding numerous studies that have utilized mutation of this critical residue for site deactivation.
A three‐dimensional model of aromatase cytochrome P450
Authors: Graham‐Lorence Sandra , Peterson Julian A. , Amarneh Bilal , Simpson Evan R. , White Ronald E. 
Published: June 2010

AbstractP450 hemeproteins comprise a large gene superfamily that catalyzes monooxygenase reactions in the presence of a redox partner. Because the mammalian members are, without exception, membrane‐bound proteins, they have resisted structure‐function analysis by means of X‐ray crystallographic methods. Among P450‐catalyzed reactions, the aromatase reaction that catalyzes the conversion of C19 steroids to estrogens is one of the most complex and least understood. Thus, to better understand the reaction mechanism, we have constructed a three‐dimensional model of P450arom not only to examine the active site and those residues potentially involved in catalysis, but to study other important structural features such as substrate recognition and redox‐partner binding, which require examination of the entire molecule (excepting the putative membrane‐spanning region). This model of P450arom was built based on a “core structure” identified from the structures of the soluble, bacterial P450s (P450cam, P450terp, and P450BM‐P) rather than by molecular replacement, after which the less conserved elements and loops were added in a rational fashion. Minimization and dynamic simulations were used to optimize the model and the reasonableness of the structure was evaluated. From this model we have postulated a membrane‐associated hydrophobic region of aliphatic and aromatic residues involved in substrate recognition, a redoxpartner binding region that may be unique compared to other P450s, as well as residues involved in active site orientation of substrates and an inhibitor of P450arom, namely vorozole. We also have proposed a scheme for the reaction mechanism in which a “threonine switch” determines whether oxygen insertion into the substrate molecule involves an oxygen radical or a peroxide intermediate.
pH dependence of the stability of barstar to chemical and thermal denaturation
Authors: Khurana Ritu , Hate Anita T. , Nath Utpal , Udgaonkar Jayant B. 
Published: June 2010

AbstractEquilibrium unfolding of barstar with guanidine hydrochloride (GdnHCl) and urea as denaturants as well as thermal unfolding have been carried out as a function of pH using fluorescence, far‐UV and near‐UV CD, and absorbance as probes. Both GdnHCl‐induced and urea‐induced denaturation studies at pH 7 show that barstar unfolds through a two‐state F ⇌ U mechanism and yields identical values for ΔGU the free energy difference between the fully folded (F) and unfolded (U) forms, of 5.0 ± 0.5 kcal·mol−1 at 25 °C. Thermal denaturation of barstar also follows a two‐state F ⇌ U unfolding transition at pH 7, and the value of ΔGU at 25 °C is similar to that obtained from chemical denaturation. The pH dependence of denaturation by GdnHCl is complex. The Cm value (midpoint of the unfolding transition) has been used as an index for stability in the pH range 2–10, because barstar does not unfold through a two‐state transition on denaturation by GdnHCl at all pH values studied. Stability is maximum at pH 2–3, where barstar exists in a molten globule‐like form that forms a large soluble oligomer. The stability decreases with an increase in pH to 5, the isoelectric pH of the protein. Above pH 5, the stability increases as the pH is raised to 7. Above pH 8, it again decreases as the pH is raised to 10. The decrease in stability from pH 7 to 5 in wild‐type (wt) barstar, which is shown to be characterized by an apparent pKa of 6.2 ± 0.2, is not observed in H17Q, a His 17 ± Gln 17 mutant form of barstar. This decrease in stability has therefore been correlated with the protonation of His 17 in barstar. The decrease in stability beyond pH 8 in wt barstar, which is characterized by an apparent pKa of 9.2 ± 0.2, is not detected in BSCCAA, the Cys 40 Cys 82 → Ala 40 Ala 82 double mutant form of barstar. Thus, this decrease in stability has been correlated with the deprotonation of at least one of the two cysteines present in wt barstar. The increase in stability from pH 5 to 3 is characterized by an apparent pKa of 4.6 ± 0.2 for wt barstar and BSCCAA, which is similar to the apparent pKa that characterizes the structural transition leading to the formation of the A form. The use of Cm as an index of stability has been supported by thermal denaturation studies. In the pH range where both chemical denaturation and thermal denaturation studies were possible, both Cm and Tm, the midpoint of a thermal denaturation curve displays similar trends. Very high pH (pH 12) is shown to completely unfold the protein in a fully reversible manner.
Crystallization and preliminary X‐ray crystallographic studies on Type III antifreeze protein
Authors: Jia Zongchao , Deluca Carl I. , Davies Peter L. 
Published: June 2010

AbstractType III antifreeze protein, more specifically the recombinant QAE‐Sephadex‐binding isoform, has been crystallized in 50–55% saturated ammonium sulfate, 0.1 M sodium acetate, pH 4.0–4.5. The resultant crystals belong to the ortho‐rhombic space group P212121 with a = 32.60 Å, b = 39.00 Å, and c = 46.57 Å and diffract to at least 1.7 Å. A set of 1.7‐Å native data has been collected, with completeness 93.4% and Rsvm of 0.069. Initial screening for heavy‐atom derivatives has yielded a Pt‐bound derivative.
Generating stereochemically acceptable protein pathways
Authors: Farrell Daniel W. , Speranskiy Kirill , Thorpe M. F. 
Published: June 2010

AbstractWe describe a new method for rapidly generating stereochemically acceptable pathways in proteins. The method, called geometric targeting, is publicly available at the webserver http://pathways.asu.edu, and includes tools for visualization of the pathway and creating movie files for use in presentations. The user submits an initial structure and a target structure, and a pathway between the two input states is generated automatically. Besides visualization, the structural quality of the pathways makes them useful as input pathways into pathway refinement techniques and further computations. The approach in geometric targeting is to gradually change the system's RMSD relative to the target structure while enforcing a set of geometric constraints. The generated pathways are not minimum free energy pathways, but they are geometrically plausible pathways that maintain good covalent bond distances and angles, keep backbone dihedral angles in allowed Ramachandran regions, avoid eclipsed side‐chain torsion angles, avoid non‐bonded overlap, and maintain a set of hydrogen bonds and hydrophobic contacts. Resulting pathways for over 20 proteins featuring a wide variety of conformational changes are reported here, including the very large GroEL complex. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Quantum chemical studies of some rhodanine azosulpha drugs as corrosion inhibitors for mild steel in acidic medium
Authors: Ebenso Eno E. , Arslan Taner , Kandemirli Fatma , Caner Necmettin , Love Ian 
Published: July 2010

AbstractThe density functional theory (DFT) at the B3LYP/6‐31G (d,p) and B3LYP/6‐311G(d,p) basis set levels and ab initio calculations using the HF/6‐31G (d,p) and HF/6‐311G(d,p) methods were performed on four rhodanine azosulpha drugs (namely 5‐sulfadiazineazo‐3‐phenyl‐2‐thioxo‐4‐thiazolidinone, 5‐ sulfamethazineazo‐3‐phenyl‐2‐thioxo‐4‐thiazolidinone, 5‐sulfadimethoxineazo‐3‐phenyl‐2‐thioxo‐ 4‐thiazolidinone, and 5‐sulfamethoxazoleazo‐3‐phenyl‐2‐thioxo‐4‐thiazolidinone) used as corrosion inhibitors for mild steel in acidic medium to determine the relationship between the molecular structure of the rhodanine azosulpha drugs and inhibition efficiency(%IE). The quantum chemical parameters/descriptors, namely, EHOMO (highest occupied molecular orbital energy), ELUMO (lowest unoccupied molecular orbital energy), the energy difference (ΔE) between EHOMO and ELUMO, dipole moment (μ), electron affinity (A), ionization potential (I), the absolute electronegativity (X), absolute hardness (η), softness (σ), polarizability (α), the Mulliken charges, and the fraction of electrons (ΔN) transfer from inhibitors to iron, were calculated and correlated with the experimental %IE. Quantitative structure activity relationship (QSAR) approach has been used, and a composite index of some quantum chemical parameters/descriptors was performed to characterize the inhibition performance of the studied molecules. The results showed that the inhibition efficiency (%IE) of the rhodanine azo sulfa drugs studied was closely related to some of the quantum chemical parameters/descriptors but with varying degrees of correlation coefficient (R2). The %IE also increased with the increase in EHOMO and decrease in EHOMO−ELUMO; and the areas containing N atoms are the most possible sites for bonding to the metal iron surface by donating electrons to the metal. The HOMO orbitals consist of 61.73–63.04% double bonded S atom (7(S)), and most of the rest are concentrated on the rhodanine group; so, the rhodanine molecule plays an important role in bonding of sulfa drugs with metal atom in the corrosion process. The calculated/estimated %IE of the compounds studied was found to be close to the experimental %IE. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Adducts of acylphloroglucinols with explicit water molecules: Similarities and differences across a sufficiently representative number of structures
Authors: Mammino Liliana , Kabanda Mwadham M. 
Published: June 2010

AbstractAcylphloroglucinols constitute a broad class of compounds, derivatives of 1,3,5‐trihydroxybenzene, characterized by at least one COR group and exhibiting a variety of biological activities. The presence of several hydrogen bond donor or acceptor sites (the three phenol OH of the phloroglucinol moiety and the sp2 O of the COR group), and their comparatively close spacing, makes the study of adducts with explicit water molecules particularly interesting, because it is possible to consider adducts in which water molecules surround the entire acylphloroglucinol molecule, or a large part of it, providing expectedly realistic images of possible arrangements of water molecules in the close vicinity of the acylphloroglucinol molecule in the aqueous medium. This work considers a number of different monomeric structures sufficiently representative of the broad structural variety of acylphloroglucinols and considers adducts of all the relevant conformers for each structure. Calculations use the HF/6‐31G(d,p) level because of affordability reasons in view of the adducts' size. The results: show that the intramolecular hydrogen bond (IHB) between the sp2 O of COR and an ortho OH does not break on competition with solute–solvent intermolecular H‐bonding; highlight general trends and trends related to specific geometry features of the conformers; enable an interpretation of the additional solvent stabilization of the conformers without IHBs, observed from polarizable continuum model results in water solution; and highlight the significance, for this class of compounds, of considering adducts in whichthe water molecules directly H‐bonded to the central molecule are bridged by other water molecules, to approximate a continuous layer. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2378–2390, 2010
Hydrogen storage inside a toroidal carbon nanostructure C120: Density functional theory computer simulation
Authors: Cruz‐Torres A. , Castillo‐Alvarado F. DE L. , Ortíz‐López J. , Arellano J. S. 
Published: June 2010

AbstractAb initio density functional calculations were performed for a toroidal carbon C120 nanostructure. Hydrogen molecules, n = 1–15, were added inside the nanotorus and for each one of these systems a geometry optimization was obtained. The cohesive energy shows that these structures are energetically stable. For example, the binding energies are −34.95 and −36.19 Hartrees and the interatomic distances HH are 0.753 and 0.772 Å for 1 and 14 molecules, respectively. Considering only molecular hydrogen, we have always seen so far weak physisorption into the C120 nanotorus. There is no chemisorption until the number oh hydrogen molecules are increased to 14. In this case, four hydrogen atoms are chemisorbed. With 15 molecules, there are 10 hydrogen atoms chemisorbed just at the inner nanotorus surface forming 10 HC bondings with bond length close to that in methane. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2495–2508, 2010
Modeling formation of molecules in the interstellar medium by radical reactions with polycyclic aromatic hydrocarbons
Authors: Bentarcurt Yenner , Ruette Fernando , Sánchez Morella 
Published: June 2010

AbstractAdsorptions of CH°2, CH°3, NH°2, and OH° radicals and molecule formation on a partially hydrogenated surface of a polycyclic aromatic hydrocarbon (PAH) (C24H27+) were modeled. It was found that radical adsorptions are feasible with important modifications of surface bond strengths and bond distances. Adsorbed hydrogen may diffuse due to adsorbate‐surface interactions. Formations of CH4, NH3, H2O, CH3NH2, and CH3OH were studied by Eley‐Rideal (ER) and Langmuir‐Hishelwood (LH) mechanisms. Potential energetic surfaces were performed for both mechanisms and the ER presents lower reaction energy barriers than the LH one, in all cases. Parametric quantum program (CATIVIC) was employed and comparisons with DFT results were performed. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2560–2572, 2010
DFT study of polymorphism of the DNA double helix at the level of dinucleoside monophosphates
Authors: Poltev Valeri I. , Anisimov Victor M. , Danilov Victor I. , van Mourik Tanja , Deriabina Alexandra , González Eduardo , Padua Maria , Garcia Dolores , Rivas Francisco , Polteva Nina 
Published: June 2010

AbstractWe apply DFT calculations to deoxydinucleoside monophosphates (dDMPs) which represent minimal fragments of the DNA chain to study the molecular basis of stability of the DNA duplex, the origin of its polymorphism and conformational heterogeneity. In this work, we continue our previous studies of dDMPs where we detected internal energy minima corresponding to the “classical” B conformation (BI‐form), which is the dominant form in the crystals of oligonucleotide duplexes. We obtained BI local energy minima for all existing base sequences of dDMPs. In the present study, we extend our analysis to other families of DNA conformations, successfully identifying A, BI, and BII energy minima for all dDMP sequences. These conformations demonstrate distinct differences in sugar ring puckering, but similar sequence‐dependent base arrangements. Internal energies of BI and BII conformers are close to each other for nearly all the base sequences. The dGpdG, dTpdG, and dCpdA dDMPs slightly favor the BII conformation, which agrees with these sequences being more frequently experimentally encountered in the BII form. We have found BII‐like structures of dDMPs for the base sequences both existing in crystals in BII conformation and those not yet encountered in crystals till now. On the other hand, we failed to obtain dDMP energy minima corresponding to the Z family of DNA conformations, thus giving us the ground to conclude that these conformations are stabilized in both crystals and solutions by external factors, presumably by interactions with various components of the media. Overall the accumulated computational data demonstrate that the A, BI, and BII families of DNA conformations originate from the corresponding local energy minimum conformations of dDMPs, thus determining structural stability of a single DNA strand during the processes of unwinding and rewinding of DNA. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem 110:2548–2559, 2010
A system dynamics approach to jurisdictional conflict between a major and a minor healthcare profession
Authors: McGregor Marion 
Published: June 2010

AbstractThe purpose of this research was to evaluate strategies that a minor profession might successfully undertake to gain market share held by a dominant player when a jurisdiction is contested. A case study approach positing Medicine as the dominant (major) profession and chiropractic as the competitor (minor profession) was used in combination with System Dynamics modelling. Informed by theory of inter‐professional competition, two strategies were hypothesized to aid a minor profession in gaining or securing market share. The first was an increase in abstract knowledge and the second was an increase in professional association membership. In addition, it was hypothesized that an increase in supply of the dominant profession would adversely affect the minor profession's bid for jurisdictional control, as would pressure on the major profession from external sources such as health management. It was concluded that for the relationships explored, simulation results favoured Medicine's monopoly power. Copyright © 2010 John Wiley & Sons, Ltd.
Orthogonal series density estimation
Authors: Efromovich Sam 
Published: June 2010

AbstractOrthogonal series density estimation is a powerful nonparametric estimation methodology that allows one to analyze and present data at hand without any prior opinion about shape of an underlying density. The idea of construction of an adaptive orthogonal series density estimator is explained on the classical example of a direct sample from a univariate density. Data‐driven estimators, which have been used for years, as well as recently proposed procedures, are reviewed. Orthogonal series estimation is also known for its sharp minimax properties which are explained. Furthermore, applications of the orthogonal series methodology to more complicated settings, including censored and biased data as well as estimation of the density of regression errors and the conditional density, are also presented. Copyright © 2010 John Wiley & Sons, Inc.This article is categorized under:

Statistical and Graphical Methods of Data Analysis > Density Estimation
Prognostic Value of Body Mass Index on Short‐Term and Long‐Term Outcome after Resection of Esophageal Cancer
Authors: Grotenhuis B. A. , Wijnhoven B. P. L. , Hötte G. J. , van der Stok E. P. , Tilanus H. W. , van Lanschot J. J. B. 
Published: July 2010

AbstractIntroductionCachexia and obesity have been suggested to be risk factors for postoperative complications. However, high body mass index (BMI) might result in a higher R0‐resection rate because of the presence of more fatty tissue surrounding the tumor. The purpose of this study was to investigate whether BMI is of prognostic value with regard to short‐term and long‐term outcome in patients who undergo esophagectomy for cancer.MethodsIn 556 patients who underwent esophagectomy (1991–2007), clinical and pathological outcome were compared between different BMI classes (underweight, normal weight, overweight, obesity).ResultsOverall morbidity, mortality, and reoperation rate did not differ in underweight and obese patients. However, severe complications seemed to occur more often in obese patients (p = 0.06), and the risk for anastomotic leakage increased with higher BMI (12.5% in underweight patients compared with 27.6% in obese patients, p = 0.04). Histopathological assessment showed comparable pTNM stages, although an advanced pT stage was seen more often in patients with low/normal BMI (p = 0.02). A linear association between BMI and R0‐resection rate was detected (p = 0.02): 60% in underweight patients compared with 81% in obese patients. However, unlike pT‐stage (p < 0.001), BMI was not an independent predictor for R0 resection (p = 0.12). There was no significant difference in overall or disease‐free 5‐year survival between the BMI classes (p = 0.25 and p = 0.6, respectively).ConclusionsBMI is not of prognostic value with regard to short‐term and long‐term outcome in patients who undergo esophagectomy for cancer and is not an independent predictor for radical R0 resection. Patients oncologically eligible for esophagectomy should not be denied surgery on the basis of their BMI class.
Video‐Assisted Bilateral Neck Exploration in Patients with Primary Hyperparathyroidism and Failed Localization Studies
Authors: Alesina Pier F. , Singaporewalla Reyaz M. , Walz Martin K. 
Published: July 2010

AbstractBackgroundIn primary hyperparathyroidism (pHPT) positive preoperative localization studies are accepted as a precondition for applying minimally invasive surgical techniques. Without localization, open bilateral neck exploration (BNE) is considered the standard option. Thepresent study analyzes the feasibility and effectiveness of minimally invasive video‐assisted BNE in patients with pHPT and negative or discordant localization studies.MethodsFrom a prospective series of 380 minimally invasive video‐assisted parathyroidectomies (MIVAP) performed in 367 patients for pHPT (1999–2009), 68 patients (10 male, 58 female; mean age: 58 years) were selected. These patients had failed localization studies and underwent BNE with the MIVAP technique. Operative time, complications, conversions to open technique, and cure rate were determined.ResultsMean operative time was 52 ± 26 min (range: 20–180 min). MIVAP with BNE was successfully completed in 66 (97%) patients with two conversions to open technique. Recurrent laryngeal nerve palsy occurred in one patient. Biochemical cure was achieved in 67 patients (98.5%), in 65 patients (95.5%) after the first operation and in two more patients by video‐assisted re‐exploration on the first postoperative day. One patient remained with persistent disease even after repeated open BNE.ConclusionsIn experienced hands, video‐assisted BNE with the MIVAP technique, for pHPT and failed localization studies, is feasible, safe, and gives results equivalent to the conventional open technique.