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At least 415 records · Page 23Linked to original sources
PubMed2005

Measurements of internal distance changes of the 30S ribosome using FRET with multiple donor-acceptor pairs: quantitative spectroscopic methods.

We present analytical and experimental procedures for determining distance changes within the 30 S subunit of the Escherichia coli ribosome using Förster resonance energy transfer (FRET). We discuss ways to contend with complexities when using FRET to measure distance changes within large multi-subunit macromolecular complexes, such as the ribosome. Complications can arise due to non-stoichiometric labeling of donor and acceptor probes, as well as environmental effects that are specific to each conjugation site. We show how to account for changes in extinction coefficients, quenching, labeling stoichiometry and other variations in the spectroscopic properties of the dye to enable more accurate calculation of distances from FRET data. We also discuss approximations that concern the orientation of the transition moments of the two dye molecules, as well as the impact of other errors in the measurement of absolute distances. Thirteen dye-pair locations with different distances using 18 independent FRET pairs conjugated to specific 30 S protein residues have been used to determine distance changes within the 30 S subunit upon association with the 50 S subunit, forming the 70 S ribosome. Here, we explain the spectroscopic methods we have used, which should be of general interest in studies that aim at obtaining quantitative distance information from FRET.

Crystallography, X-Ray↗
PubMed1999

Assessment of central and peripheral fusion and near and distance stereoacuity in intermittent exotropic patients before and after strabismus surgery.

PURPOSE: To determine whether central fusion and distance stereoacuity are useful as objective measures in assessing the need for and success of surgery for intermittent exotropia (X[T]). METHODS: A prospective, institutional, clinical trial was conducted of 26 consecutive patients with X(T) who were undergoing strabismus surgery in whom fusion (central and peripheral) and stereoacuity (at near and distance) were assessed preoperatively and postoperatively, as well as in 112 normal subjects. To obtain accurate measurements with sensory tests, the lower age was limited to 5 years for inclusion. A successful surgical alignment was defined as an exotropia of 10 prism diopters or less at 6 m. Sensory and motor outcome measures were determined 1 year after surgery. RESULTS: The successful surgical alignment rate was 69%. All patients with X(T) demonstrated peripheral fusion, whereas 35% demonstrated central suppression preoperatively and postoperatively. Central fusion was not predictive of surgical outcome (P = .078); however, there was a trend toward less surgical success in patients with central suppression. Patients with X(T) exhibited good near stereoacuity before and after surgery. Distance stereoacuity in patients with X(T) preoperatively was significantly diminished compared with normal subjects (P < .001) and was improved in 58% postoperatively. Patients who achieved successful surgical alignment had a greater likelihood of demonstrating distance stereoacuity improvement postoperatively than patients who failed to achieve successful surgical alignment (P = .003). Patients with central suppression were unlikely to improve their distance stereoacuity postoperatively (P = .014). CONCLUSIONS: Successful surgery may improve distance stereoacuity. Better distance stereoacuity and central fusion are frequently associated with better surgical success in X(T).

Adolescent↗
PubMed2001

[Effect of naftidrofuryl on physiological walking distance in patients with intermittent claudication].

PURPOSE: To evaluate the physiological walking distance measured with the Peripheral Arterial Disease Holter Control device (PADHOC) after 12 months of treatment with naftidrofuryl in a double blind placebo controlled, parallel group study, in patients presenting with intermittent claudication. MATERIAL AND METHODS: The outpatients selected were of both sexes, aged 40 to 80, with a chronic, stable intermittent claudication and an ankle brachial index between 0.60 and 0.90. They received naftidrofuryl 200 mg tid or placebo for 12 months. Outcome measures included physiological painfree and maximal walking distances using the PADHOC device. The principle of this device is the measurement of the intermalleolar distances using ultrasound telemetry. The PADHOC measures the walking distance and the speed profile in an ambulatory subject. RESULTS: 182 patients were randomised and 168 entered the intention to treat analysis. The two groups were well matched for demographic variables, risk factors and history of vascular disease. After 12-month treatment, patients who received naftidrofuryl had a 107% improvement of geometric physiological pain-free walking distance versus 12% in the placebo group (P < 0.001) and 74% improvement of geometric maximal physiological walking distance versus 1% in the placebo group (P < 0.001). CONCLUSION: This study demonstrates the efficacy of naftidrofuryl versus placebo in patients with intermittent claudication using a new device measuring the walking distances of the patients in a more physiological way than the treadmill test.

Adult↗
PubMed2004

Optimal distance of malignant negative margin in excision of nonsmall cell lung cancer: a multicenter prospective study.

BACKGROUND: Complete excision of nonsmall cell lung cancer is necessary during a limited resection procedure, as a malignant positive margin can lead to margin relapse. Because there is scant information available regarding the optimal size of a malignant negative margin, we conducted a multicenter, prospective study to more fully elucidate this area of concern. METHODS: Two hundred five pulmonary tumors (22 nonsmall cell lung cancers and 183 undiagnosed lesions) were excised, of which 118 nonsmall cell lung cancer lesions were analyzed. Malignant status was considered positive when either a cytologic or histologic technique revealed the margin to be malignant. Maximum tumor diameter (from 4 to 45 mm with an average of 15.3 mm), margin distance (from 0 to 25 mm with an average of 9.3 mm), tumor location, extent of stapling carried out, and performance of a thoracotomy were the variables. RESULTS: Seventy-two of the sample tissues (61%) were malignant negative. The negative group had smaller maximum tumor diameter, greater margin distance, lesions in more easily resectable regions, and more often required stapling only. Using a multivariate analysis, maximum tumor diameter and margin distance were found to be independent factors. The number of malignant negative margins was 7/7 (100%) when the margin distance was greater than 20 mm, and the number of malignant negative margins was 21 of 21 (100%) when the resected tumors had a margin distance greater than the maximum tumor diameter. CONCLUSIONS: Malignant positive margins were not found when the margin distance was greater than the maximum tumor diameter, which was considered to be the optimal margin distance for prevention against margin relapse.

Aged↗
PubMed1999

Industrial inspection performance depends on both viewing distance and oculomotor characteristics.

The influence of viewing distance and individual differences in the oculomotor resting states (dark vergence and dark focus) on both inspection performance and visual fatigue was investigated by asking 24 college students to perform a visual inspection task for 40 min twice, once with a 20 cm viewing distance and once with a 60 cm viewing distance. During the task participants visually searched enlarged images of contact lenses for six different types of defects. Lens images were presented at a constant visual angle (17.5 degrees) on a CRT. Inspection performance varied significantly across the two viewing distances: participants spent on average more than twice as much time inspecting individual lenses in the near condition (mean = 18.32 s lens(-1)) than in the far condition (mean = 7.25 s lens(-1)). Participants also reported greater visual fatigue in the near condition than in the far condition. At both viewing distances, participants who experienced relatively large inward shifts in dark vergence also tended to be slow inspectors. Neither inspection performance nor measures of fatigue were related to dark focus. These results support existing evidence against the use of near viewing distances and suggest that an oculomotor mechanism links inspection performance and visual fatigue to viewing distance.

Accommodation, Ocular↗
PubMed2003

Effects of two preparation designs and pontic distance on bending and fracture strength of fiber-reinforced composite inlay fixed partial dentures.

STATEMENT OF PROBLEM: Joint fractures observed in Targis/Vectris inlay adhesive fixed restorations may be related to the preparation design. PURPOSE: This in vitro study investigated the effects of the proximal tooth preparation design and the pontic distance on the fracture strength and the amount of bending of fiber-reinforced inlay adhesive fixed partial dentures. MATERIALS AND METHODS: Forty extracted premolars and 40 molars were embedded in a PMMA resin to represent a premolar and molar mesiodistal separation distance of 7 mm and 11 mm, respectively. Two preparation designs were used (proximal box and tub-shaped). The sample size was 10 for each group. Fiber-reinforced inlay adhesive fixed partial dentures were fabricated by use of the Targis/Vectris system and luted adhesively to the teeth with Variolink luting agent. A vertical force was loaded to the center of the fixed partial dentures at a crosshead speed of 1 mm/min. The initial bending (mm) prior to fracture was evaluated by measuring the distance the test rod moved from a 10 N preload to fracture. The differences in the mean fracture strength and the average amount of bending as a function of the preparation designs and pontic distances were compared by use of a 2-way analysis of variance (alpha=.05). The specimens were examined optically for the type of failure with a stereomicroscope. The fracture surface of the specimens was examined by scanning electron microscopy, and radiography was used to investigate the surface morphological features at the failure sites and to determine the fracture mode. A chi-square test was used to identify the differences in the debonding rates between the types of preparation designs and the pontic distance (alpha=.05). RESULTS: The mean fracture strength and the standard deviation of the fiber-reinforced inlay retained adhesive fixed partial denture group was 1368+/-212 N for the 7-mm tub group, 885+/-109 N for the 11-mm tub group, 1779+/-317 N for the 7-mm box group, and 1336+/-281 N for the 11-mm box group. The fracture strength was significantly higher in the 7-mm pontic distance (P<.001) and for the box-shaped tooth preparation (P<.001). The amount of bending was significantly greater in the 7-mm pontic distance (P=.025) and the box-shaped tooth preparation (P=.002). Debonding was observed only in premolar teeth and tub-shaped design groups. CONCLUSION: The box-shaped tooth preparation may be considered for restoration of a missing single posterior tooth with fiber-reinforced inlay adhesive fixed partial dentures.

Adhesiveness↗
PubMed1999

Distance between mitral anulus and papillary muscles: anatomic study in normal human hearts.

BACKGROUND: Preservation of the annulo-papillary muscle continuity in mitral valve replacement is important. Even in patients who require excision of the mitral apparatus, the continuity can be restored. However, there is no guide to the proper length for the resuspension. METHODS: In 57 normal cadaveric hearts, the distance from the tip of the papillary muscle to its corresponding mitral anulus was directly measured. RESULTS: The distance from the tip of the anterolateral papillary muscle to the left trigone (10-o'clock position: D10) and to the point between the anterior and the middle scallops of the mural leaflet (8-o'clock position: D8) was 23.5 +/- 3.7 mm and 23.2 +/- 3.6 mm, respectively. The distance from the tip of the posteromedial papillary muscle to the right trigone (2-o'clock position: D2) and to the point between the middle and the posterior scallops of the mural leaflet (4-o'clock position: D4) was 23.5 +/- 4.0 mm and 23.5 +/- 3.9 mm, respectively. There was no statistically significant difference among the 4 distances (P =.96). Each distance was significantly longer than the corresponding chordae tendineae (D10 vs the anterior main chorda: 17.2 +/- 3.9 mm, D8 vs the anterior cleft chorda: 14.5 +/- 3.2 mm, D2 vs the posterior main chorda: 17.9 +/- 4.3 mm, and D4 vs the posterior cleft chorda: 14.9 +/- 3.2 mm, respectively; P =.0001). The mean distance had a significant correlation with the mitral annular diameter (r = 0.31, P =.019). CONCLUSIONS: In normal hearts, the annulo-papillary muscle distances of the mitral apparatus are similar in 2-, 4-, 8-, and 10-o'clock positions and correlate with the mitral annular diameter.

Adult↗
PubMed1999

Effects of distances to hospital and GP surgery on hospital inpatient episodes, controlling for needs and provision.

Age and sex adjusted inpatient episode ratios were calculated from hospital records over a two year period for 555 census wards in Cambridgeshire, Norfolk and Suffolk, UK. Hospital episodes were divided into acute, psychiatric and geriatric specialties, and elective and emergency acute admissions were distinguished. Variations in inpatient episode ratios between wards were compared with census indicators of the 'needs' of local populations for inpatient services, measures of the local provision of hospital and other related services, and measures of the distance to the nearest general practitioner surgery and the distance to the nearest hospital. Hospital episodes were found to be strongly related to both distance measures, but the associations were partially explained by a tendency for the health status of local populations (measured by the needs indicators) to be worst in urban areas close to health services. Including needs and provision variables together with the distance variables explained most of the variations in age and sex adjusted inpatient ratios for small areas. Needs were the most important determinants of emergency acute and psychiatric inpatient rates, but service provision was more important for elective acute and geriatric inpatients. Controlling for needs and provision, distance to hospital produced 17% reduction in acute episodes, 37% reduction in psychiatric episodes and 23% reduction in geriatric episodes over the range of distances observed. Distance to nearest GP surgery reduced elective acute episodes by up to 15% after controlling for confounders. These results demonstrate that the NHS is falling short of its aim to provide fair access to services irrespective of geography, and new policies will be required if geographical inequities are to be reduced.

England↗
PubMed1996

Collimator (head) scatter at extended distances in linear accelerator-generated photon beams.

PURPOSE: A calculation formalism is proposed to predict variation of head scatter as a function of field size and treatment distance. METHODS AND MATERIALS: Assuming that the head scatter for the linear accelerator studied was contributed predominantly by the flattening filter, a formalism was devised to predict beam intensity as a function of distance from the target position. The method used the concept of an equivalent collimator field in which a given field at any distance can be equated to a field at the isocenter such that the extent of the flattening filter seen at the two positions is the same. RESULTS: The equation derived from the concept of equivalent collimator field size predicated change in head scatter with distance to within 0.5% for collimator field sizes ranging from 8 x 8 to 40 x 40 cm and distances up to 300 cm from the target. CONCLUSIONS: Considering flattening filter to be the main source of head scatter, the observed deviation from inverse square law for extended treatment distances can be accounted for by an equivalent collimator field size, which sees the same extent of the flattening filter at the isocenter as the field at the given distance.

Particle Accelerators↗
PubMed2002

Effect of distance and infusion rate on operation of Medfusion 2010 infusion pump during magnetic resonance imaging.

STUDY OBJECTIVES: To determine the accuracy and reliability of intravenous infusion, as well as magnetic resonance image effect of the Medfusion 2010 infusion pump (Medex Medical Supplies, Inc., Duluth, GA) at distances of 2, 4, 8, 12, and 16 feet from a 1.5 Tesla MRI magnet over a four-week time interval, using infusion rates that would correspond to those of propofol administration. DESIGN: Prospective, open-label study. SETTING: Radiology department MRI in an American academic medical center. INTERVENTIONS: Five infusion pumps, including one outside the MRI suite as control, were tested. Pumps were evaluated at distances of 2, 4, 8, 12, and 16 feet from a 1.5 Tesla magnet. One pump at distances of 2 and 16 feet was tested during 30 and 90 hours of operation, respectively. Three pumps at distances of 4, 8, and 12 feet were tested during 120 hours of operation. Pump batteries were recharged for 18 hours outside the MRI suite between the 6-hour test periods. Distilled, deionized water was infused from a 30-mL or 60-mL syringe via a 36-inch Medex small-bore extension set into a graduated collection cylinder at rates of 5, 10.5, 21, or 42 mL/hr. Each rate was increased to the next infusion rate level at 30-hour weekly intervals. The collection cylinder with infused water was weighed on an electronic scale accurate to within +/-0.001 g. Analysis of variance and regression analysis were used to analyze data. A p < 0.05 value was considered statistically significant. MEASUREMENTS AND MAIN RESULTS: There was no significant difference comparing the grams weight of volume measured and the mL volume visualized within and between groups at varying distances from the magnet. Increasing infusion rates resulted in corresponding increases in volume delivered irrespective of the distance from the magnet. CONCLUSIONS: The Medfusion 2010 infusion pumps were found to be reliable and accurate, without causing failure or any significant degradation of MRI images compared to control at infusion rate of 42 mL/hr at a distance of 2 feet for 30 hours; and a rate of 5.0, 10.5, 21, and 42 mL/hr at 16 feet for 90 hours; and at 4, 8, and 12 feet for 120 hours of operation.

Anesthesiology↗
PubMed1992

Distances between the antigen-binding sites of three murine antibody subclasses measured using neutron and X-ray scattering.

For three different murine immunoglobulins (IgG subclasses 1, 2a, and 2b), the distances between their antigen-binding sites have been measured using neutron scattering from deuterated antigens complexed with proteated IgG. Neutron-scattering data were measured for each antibody-antigen complex in a 41% D2O solvent. Unlike the proteated antibody molecule, the deuterated antigens are strongly contrasted against the 41% D2O solvent and give rise to a scattering profile that contains an interference term related to the distance between the deuterated antigens. For all three subclasses, the damping of this interference term, which gives information on the relative flexibility of the antigen-binding sites, indicates that a single distance is inadequate to describe the observed scattering and a distribution of distances is needed. The scattering profile has been modeled for each subclass to give the mean distance between the antigens and the variance of this distance. For all three IgG subclasses, the mean distance is between 117 and 134 A, and the variance is large (approximately 40 A), indicating a high degree of flexibility of the Fab arms. Small-angle X-ray scattering measurements on the same samples are consistent with the neutron-scattering results.

Animals↗
PubMed1989

Limited sampling of conformational space by the distance geometry algorithm: implications for structures generated from NMR data.

Calculations with a metric matrix distance geometry algorithm were performed that show that the standard implementation of the algorithm generally samples a very limited region of conformational space. This problem is most severe when only a small amount of distance information is used as input for the algorithm. Control calculations were performed on linear peptides, disulfide-linked peptides, and a double-stranded DNA decamer where only distances defining the covalent structures of the molecules (as well as the hydrogen bonds for the base pairs in the DNA) were included as input. Since the distance geometry algorithm is commonly used to generate structures of biopolymers from distance data obtained from NMR experiments, simulations were performed on the small globular protein basic pancreatic trypsin inhibitor (BPTI) that mimic calculations performed with actual NMR data. The results on BPTI and on the control peptides indicate that the standard implementation of the algorithm has two main problems: first, that it generates extended structures; second, that it has a tendency to consistently produce similar structures instead of sampling all structures consistent with the input distance information. These results also show that use of a simple root-mean-square deviation for evaluating the quality of the structures generated from NMR data may not be generally appropriate. The main sources of these problems are identified, and our results indicate that the problems are not a fundamental property of the distance geometry algorithm but arise from the implementations presently used to generate structures from NMR data. Several possible methods for alleviating these problems are discussed.

Algorithms↗
PubMed1980

Magnetic resonance measurements of intersubstrate distances at the active site of protein kinase using substitution-inert cobalt(III) and chromium(III) complexes of adenosine 5'-(beta, gamma-methylenetriphosphate).

Co3+ and Cr3+ complexes of beta, gamma-methylene-ATP (AMPPCP), which are substitution-inert substrate analogues inactive in phosphoryl transfer reactions, have been used in binding and structural studies of cAMP-dependent protein kinase. Dissociation constants of enzyme complexes with Co(NH3)4AMPPCP and CrAMPPCP and with Mn2+, which binds at an inhibitory site, were determined by electron paramagnetic resonance and by proton relaxation rate enhancement techniques. Nuclear relaxation rate measurements at 100 and 360 MHz were used to determine the distance between Mn2+ and the beta, gamma-methylene protons of Co-(NH3)4AMPPCP, yielding 7.4 +/- 0.6 A in the absence of enzyme and 5.0 +/- 0.9 A when both Mn2+ and Co-(NH3)4AMPPCP were bound to the enzyme. The effect of the paramagnetic CrAMPPCP on the electron spin relaxation time of the enzyme-bound Mn2+ was used used to calculate the distance between the two metal ions of 4.8 +/- 0.4 A. This distance and the Mn2+-methylene distance are consistent with the previous finding that the inhibitory metal bridges the enzyme to the triphosphate chain of the enzyme-bound nucleotide [Granot, J., Kondo, H., Armstrong, R. M., Mildvan, A. S., & Kaiser, E. T. (1979) Biochemistry 18, 2339]. From the paramagnetic effects on the relaxation rates of the protons of the peptide substrate Leu-Arg-Arg-Ala-Ser-Leu-Gly, distances from Mn2+ and Cr3+ to the serine methylene protons of 9.1 +/- 0.9 and 8.1 +/- 0.8 A, respectively, were calculated. These and previous measurements were used to estimate a distance of 5.3 +/- 0.7 A along the reaction coordinate between the gamma-phosphorus of ATP and the serine hydroxyl oxygen. This distance is 2 A greater than that required for molecular contact. The mechanistic implications of these findings are discussed.

Adenosine Triphosphate↗
PubMed2002

Site-directed rotational resonance solid-state NMR distance measurements probe structure and mechanism in the transmembrane domain of the serine bacterial chemoreceptor.

The serine receptor of bacterial chemotaxis is an ideal system in which to investigate the molecular mechanism of transmembrane signaling. Solid-state nuclear magnetic resonance (NMR) techniques such as rotational resonance provide a means for measuring local structure and ligand-induced structural changes in intact membrane proteins bound to native membrane vesicles. A general site-directed biosynthetic (13)C labeling strategy is used to direct the distance measurements to a specific site; the distance is measured between a unique Cys residue and a non-unique, low-abundance residue (Tyr or Phe). A (13)C-(13)C internuclear distance measurement from (13)CO(i) to (13)C beta(i + 3) at the periplasmic edge of the second membrane-spanning helix (TM2) of 5.1 +/- 0.2 A is consistent with the predicted alpha-helical structure and thus demonstrates an accurate long-distance rotational resonance measurement in the 120 kDa membrane-bound receptor. These measurements require a correction for the rotational resonance exchange between the multiple labels of the non-unique amino acid and the natural-abundance (13)C, which is critical to distance measurements in complex systems. A second (13)C-(13)C distance measurement between the transmembrane helices provides a high-resolution measurement of tertiary structure in the transmembrane region. The measured 5.0-5.3 A distance in the presence and absence of ligand is consistent with structural models for the transmembrane region and a proposed signaling mechanism in which ligand binding induces a 1.6 A translation of TM2. This approach can be used for additional measurements of the structure of the transmembrane region and to determine whether the ligand-induced motion is indeed propagated through the transmembrane helices.

Carbon Isotopes↗
PubMed2002

Protein structure determination using long-distance constraints from double-quantum coherence ESR: study of T4 lysozyme.

We report the use of a novel pulsed ESR technique for distance measurement, based on the detection of double quantum coherence (DQC), which yields high quality dipolar spectra, to significantly extend the range of measurable distances in proteins using nitroxide spin-labels. Eight T4 lysozyme (T4L) mutants, doubly labeled with methanethiosulfonate spin-label (MTSSL), have been studied using DQC-ESR at 9 and 17 GHz. The distances span the range from 20 A for the 65/76 mutant to 47 A for the 61/135 mutant. The high quality of the dipolar spectra also allows the determination of the distance distributions, the width of which can be used to set upper and lower bounds in future computational strategy. It is also demonstrated that the shape of these distributions can reveal the presence of multiple conformations of the spin-label, an issue of critical relevance to the structural interpretation of the distances. The distances and distributions found in this study are readily rationalized in terms of the known crystal structure, the characteristic conformers of the nitroxide side chains, and molecular modeling. This study sets the stage for the use of DQC-ESR for determining the tertiary structure of large proteins with just a small number of long-distance constraints.

Bacteriophage T4↗
PubMed2006

Determination of the oligomeric number and intermolecular distances of membrane protein assemblies by anisotropic 1H-driven spin diffusion NMR spectroscopy.

Determination of the high-resolution quaternary structure of oligomeric membrane proteins requires knowledge of both the oligomeric number and intermolecular distances. The centerband-only detection of exchange (CODEX) technique has been shown to enable the extraction of the oligomeric number through the equilibrium exchange intensity at long mixing times. To obtain quantitative distances, we now provide an analysis of the mixing-time-dependent CODEX intensities using the 1H-driven spin diffusion theory. The exchange curve is fit to a rate equation, where the rate constants are proportional to the square of the dipolar coupling and the spectral overlap integral between the exchanging spins. Using a number of 13C- and 19F-labeled crystalline model compounds with known intermolecular distances, we empirically determined the overlap integrals of 13C and 19F CODEX for specific spinning speeds and chemical shift anisotropies. These consensus overlap integral values can be applied to structurally unknown systems to determine distances. Applying the 19F CODEX experiment and analysis, we studied the transmembrane peptide of the M2 protein (M2TMP) of influenza A virus bound to 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine bilayers. The experiment proved for the first time that M2TMP associates as tetramers in lipid bilayers, similar to its oligomeric state in detergent micelles. Moreover, the nearest-neighbor interhelical F-F distance between (4-19F)Phe30 is 7.9-9.5 angstroms. This distance constrains the orientation and the packing of the helices in the tetrameric bundle and supports the structural model derived from previous solid-state NMR 15N orientational data. Thus, the CODEX technique presents a general method for determining the oligomeric number and intermolecular distances in the approximately 10 angstroms range in membrane proteins and other complex biological assemblies.

Anisotropy↗
PubMed2006

Molecular dynamics of apo-adenylate kinase: a distance replica exchange method for the free energy of conformational fluctuations.

A large domain motion in adenylate kinase from E. coli (AKE) is studied with molecular dynamics. AKE undergoes a large-scale rearrangement of its lid and AMP-binding domains when the open form closes over its substrates, AMP, and Mg2+-ATP, whereby the AMP-binding and lid domains come closer to the core. The third domain, the core, is relatively stable during this motion. A reaction coordinate that monitors the distance between the AMP-binding and core domains is selected to be able to compare with the results of energy transfer experiments. Sampling along this reaction coordinate is carried out by using a distance replica exchange method (DREM), where systems that differ by a restraint potential enforcing different reaction coordinate values are independently simulated with periodic attempts at exchange of these systems. Several methods are used to study the efficiency and convergence properties of the DREM simulation and compared with an analogous non-DREM simulation. The DREM greatly accelerates the rate and extent of configurational sampling and leads to equilibrium sampling as measured by monitoring collective modes obtained from a principal coordinate analysis. The potential of mean force along the reaction coordinate reveals a rather flat region for distances from the open to a relatively closed AKE conformation. The potential of mean force for smaller distances has a distinct minimum that is quite close to that found in the closed form X-ray structure. In concert with a decrease in the reaction coordinate distance (AMP-binding-to-core distance) the lid-to-core distance of AKE also decreases. Therefore, apo AKE can fluctuate from its open form to conformations that are quite similar to its closed form X-ray structure, even in the absence of its substrates.

Adenosine Monophosphate↗
PubMed2004

Gene-centromere distances of allozyme loci in even- and odd-year pink salmon, (Oncorhynchus gorbuscha).

We produced gynogenetic progeny families to estimate gene-centromere (G-C) distances of allozyme loci in even-year and odd-year pink salmon (Oncorhynchus gorbuscha). G-C distances of 37 loci distributed on a chromosome ranged from 1 cM at LDH-A1* to 49 cM at ADA-2*, DIA-2*, and sMDH-B1,2*. The distribution of the G-C distances along the chromosome arm was not even and appears telomeric. Eight loci in even-year and seven in odd-year showed high G-C distances (>45 cM), indicating that one crossover per chromosome arm is usual in pink salmon. Variation was observed in the results from different families; 14 loci out of 21 tested, showed heterogeneity. At mAH-3*, G-C distances from five odd-year families ranged from 6 to 37 cM; the widest range observed in this study. At isoloci such as sMDH-A 1,2* and sMDH-B1,2* the distances from different families were grouped into statistically discrete distributions, suggesting that it may be a reflection polymorphism at both isoloci. It appears G-C distances in salmonid species are well conserved with some minor differences.

Animals↗