PubMed Health⌕ Search

Biomedical subjects

H X Zhou

Publications and source records attributed to H X Zhou.

34 records · Page 2Linked to original sources
PubMed1996

In vitro evolution of thermodynamically stable turns.

To determine the role of primary structure in specifying turns, random sequences (guests) were substituted for the native turn sequences in a series of proteins (hosts) of differing thermodynamic stabilities.The fraction of inserts that result in active proteins is measured as a function of the stability of the host and temperature. With a highly stable host, more than half of the inserts give functional proteins. However, a smaller fraction of sequences supports folding as the stability of the host decreases, and the temperature increases. The sequences of many of the selected inserts resemble the wild-type turn, and those that diverge match other established turn preferences. Thermodynamic measurements show that turn sequences selected under stringent conditions result in the most stable proteins. Thus, beta-turns appear to be under evolutionary pressure favouring thermodynamically stable structures.

Amino Acid Sequence↗
PubMed1995

Protein design: a hierarchic approach.

The de novo design of peptides and proteins has recently emerged as an approach for investigating protein structure and function. Designed, helical peptides provide model systems for dissecting and quantifying the multiple interactions that stabilize secondary structure formation. De novo design is also useful for exploring the features that specify the stoichiometry and stability of alpha-helical coiled coils and for defining the requirements for folding into structures that resemble native, functional proteins. The design process often occurs in a series of discrete steps. Such steps reflect the hierarchy of forces required for stabilizing tertiary structures, beginning with hydrophobic forces and adding more specific interactions as required to achieve a unique, functional protein.

Amino Acid Sequence↗
PubMed1995

Demonstration of positionally disordered water within a protein hydrophobic cavity by NMR.

The presence and location of water of hydration (that is, bound water) in the solution structure of human interleukin-1 beta (hIL-1 beta) was investigated with water-selective two-dimensional heteronuclear magnetic resonance spectroscopy. It is shown here that in addition to water at the surface of the protein and ordered internal water molecules involved in bridging hydrogen bonds, positionally disordered water is present within a large, naturally occurring hydrophobic cavity located at the center of the molecule. These water molecules of hydration have residency times in the range of 1 to 2 nanoseconds to 100 to 200 microseconds and can be readily detected by nuclear magnetic resonance (NMR). Thus, large hydrophobic cavities in proteins may not be truly empty, as analysis of crystal structures appears to show, but may contain mobile water molecules that are crystallographically invisible but detectable by NMR.

Electrochemistry↗
PubMed1995

Structural analysis of the N- and C-termini in a peptide with consensus sequence.

We present a structural analysis of a peptide, the sequence of which includes amino acids that show preferences for specific positions near the N- and C-termini in protein helices. This peptide has the sequence ac-YMSEDELKAAEAAFKRHGVP-amide, which includes a strong version of an N-terminal Harper-Rose capping box structure as well as a Gly located close to the C-terminus designed to elucidate its role in C-terminal capping. The sequence of five residues at the middle is inserted to separate effects at the two ends via a helix-stabilizing linker. Application of a simulated annealing procedure using interproton distance constraints derived from 1H NOESY experiments in water reveals the presence of a C-terminal structure in this model. The C-terminus forms a folded back structure in a significant fraction of structures generated by the annealing, in most of which Gly assumes an alpha L conformation. This structure occurs within a highly flexible region of the molecule and hence is occupied only a fraction of the time.

Amino Acid Sequence↗
PubMed1995

Calculation of translational friction and intrinsic viscosity. I. General formulation for arbitrarily shaped particles.

A general method for calculating translational friction and intrinsic viscosity is developed through exploiting relations between hydrodynamics and electrostatics. An approximate relation xi = 6 pi eta 0C between the translational friction coefficient xi of a particle (eta 0: solvent viscosity) and its capacitance C was derived previously. This involved orientationally preaveraging the Oseen tensor, but the result was found to be very accurate. Based on preaveraging, we find that the intrinsic viscosity [eta] of a particle can be estimated from its polarizability alpha through [eta] = 3/4 alpha + 1/4 Vp, where Vp is the volume of the particle. Both the capacitance and the polarizability can be obtained in a single calculation using the boundary-element technique. An efficient approach is thus found for estimating [eta], a quantity that is very useful in practice because of its sensitivity to particle shape but is notoriously difficult to calculate. Illustrative calculations on ellipsoids, cylinders, and dumbbells demonstrate both the accuracy of the approximate relations and the efficiency of the present method.

Computer Simulation↗
PubMed1994

Alpha helix capping in synthetic model peptides by reciprocal side chain-main chain interactions: evidence for an N terminal "capping box".

A significant fraction of the amino acids in proteins are alpha helical in conformation. Alpha helices in globular proteins are short, with an average length of about twelve residues, so that residues at the ends of helices make up an important fraction of all helical residues. In the middle of a helix, H-bonds connect the NH and CO groups of each residue to partners four residues along the chain. At the ends of a helix, the H-bond potential of the main chain remains unfulfilled, and helix capping interactions involving bonds from polar side chains to the NH or CO of the backbone have been proposed and detected. In a study of synthetic helical peptides, we have found that the sequence Ser-Glu-Asp-Glu stabilizes the alpha helix in a series of helical peptides with consensus sequences. Following the report by Harper and Rose, which identifies SerXaaXaaGlu as a member of a class of common motifs at the N termini of alpha helices in proteins that they refer to as "capping boxes," we have reexamined the side chain-main chain interactions in a variant sequence using 1H NMR, and find that the postulated reciprocal side chain-backbone bonding between the first Ser and last Glu side chains and their peptide NH partners can be resolved. Deletion of two residues N terminal to the Ser-Glu-Asp-Glu sequence in these peptides has no effect on the initiation of helical structure, as defined by two-dimensional (2D) NMR experiments on this variant.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Simulation of the kinetics of ligand binding to a protein by molecular dynamics: geminate rebinding of nitric oxide to myoglobin.

We have begun to use molecular dynamics to simulate the kinetics of nitric oxide rebinding to myoglobin after photodissociation. Rebinding was simulated using a potential function that switches smoothly between a nonbinding potential and a binding potential as a function of the position and orientation of the ligand, with no barrier arising from the crossing of potential surfaces of different electron spin. In 96 of 100 trajectories, the ligand rebound in < 15 ps. The kinetic progress curve was obtained by determining the time in each trajectory at which the ligand rebound and then calculating the fraction of unbound ligands as a function of time. The curve can be well reproduced by a simple model based on the dynamics of a Langevin particle moving on a one-dimensional potential of mean force calculated from nonreactive protein trajectories. The rate of escape from the energy well adjacent to the heme is in good agreement with the value calculated from experimental data, suggesting that a multiple-well model provides a plausible explanation for the nonexponential rebinding kinetics. A transition-state analysis suggests that protein conformational relaxation coupled to the displacement of the iron from the heme plane is an unlikely cause for the nonexponential rebinding of nitric oxide.

Computer Simulation↗
PubMed1993

Capping interactions in isolated alpha helices: position-dependent substitution effects and structure of a serine-capped peptide helix.

The influence of an amino acid on the stability of alpha-helical structure depends on the position of the residue in the helix with respect to the ends. Short alpha helices in proteins are stabilized both by H-bonding of the main-chain NH and CO groups and by capping interactions between side chains and unfulfilled peptide groups at the N and C termini. Peptide models based on consensus position-dependent helix sequences allow one to model capping effects in isolated helices and to establish a base line for these interactions in proteins. We report here an extended series of substitutions in the cap positions of our peptide models and the solution structure of peptide S3, with serine at the N-cap position defined as the N-terminal residue with partly helix and partly coil conformation. The resulting model, determined by 2D 1H NMR, is consistent with a structure at the N-cap involving H-bonding between the serine gamma oxygen and the peptide NH of the glutamic acid residue three amino acids toward the C terminus. A bifurcated H-bond of Ser O gamma with the NH of Asp5 is possible also, since this group is within interacting distance. This provides direct evidence that specific side-chain interactions with the main chain stabilize isolated alpha-helical structure.

Amino Acid Sequence↗
PubMed1993

Boundary element solution of macromolecular electrostatics: interaction energy between two proteins.

The boundary element technique is implemented to solve for the electrostatic potential of macromolecules in an ionic solution. This technique entails solving surface integral equations that are equivalent to the Poisson and the Poisson-Boltzmann equations governing the electrostatic potential inside the macromolecules and and in the solvent. A simple but robust method is described for discretizing the macromolecular surfaces in order to approximate the integral equations by linear algebraic equations. Particular attention is paid to the interaction energy between two macromolecules, and an iterative procedure is devised to make the calculation more efficient. This iterative procedure is illustrated in the electron transfer system of cytochrome c and cytochrome c peroxidase.

Cytochrome c Group↗
PubMed1993

Brownian dynamics study of the influences of electrostatic interaction and diffusion on protein-protein association kinetics.

A unified model is presented for protein-protein association processes that are under the influences of electrostatic interaction and diffusion (e.g., protein oligomerization, enzyme catalysis, electron and energy transfer). The proteins are modeled as spheres that bear point charges and undergo translational and rotational Brownian motion. Before association can occur the two spheres have to be aligned properly to form a reaction complex via diffusion. The reaction complex can either go on to form the product or it can dissociate into the separate reactants through diffusion. The electrostatic interaction, like diffusion, influences every step except the one that brings the reaction complex into the product. The interaction potential is obtained by extending the Kirkwood-Tanford protein model (Tanford, C., and J. G. Kirkwood. 1957. J. Am. Chem. Soc. 79:5333-5339) to two charge-embedded spheres and solving the consequent equations under a particular basis set. The time-dependent association rate coefficient is then obtained through Brownian dynamics simulations according an algorithm developed earlier (Zhou, H.-X. 1990. J. Phys. Chem. 94:8794-8800). This method is applied to a model system of the cytochrome c and cytochrome c peroxidase association process and the results confirm the experimental dependence of the association rate constant on the solution ionic strength. An important conclusion drawn from this study is that when the product is formed by very specific alignment of the reactants, as is often the case, the effect of the interaction potential is simply to scale the association rate constant by a Boltzmann factor. This explains why mutations in the interface of the reaction complex have strong influences on the association rate constant whereas those away from the interface have minimal effects. It comes about because the former mutations change the interaction potential of the reaction complex significantly and the latter ones do not.

Algorithms↗
PubMed1991

Effect of experimental acute hypertension of the biliary tract on hemodynamics and activity of the major splanchnic nerve in rabbits.

An experimental study of the effect of acute biliary hypertension on hemodynamics and activity of the major splanchnic nerve was conducted in Japanese big ear white rabbits. A catheter with an inflatable rubber bag fixed to its anterior end was inserted into the extrahepatic biliary duct via the duodenum, and a biliary high pressure of 20 kFa (150 mmHg) was created and maintained for 2 h by inflating the bag with water. The right major splanchnic nerve was isolated and the impulse frequencies of the nerve were recorded during the study. Arterial blood pressure was also dynamically monitored. A significant fall of the arterial blood pressure (P less than 0.01) and an increase in impulse frequency of the nerve (P less than 0.01) were found in this "simple type" acute biliary high pressure without infection. Biliary decompression immediately eliminated these abnormalities (P less than 0.01). The drop in blood pressure was much less prominent if the right splanchnic nerve was blocked prior to biliary high pressure.

Animals↗
PubMed1990

Theoretical description of the spatial dependence of sickle hemoglobin polymerization.

We have generalized the double nucleation mechanism of Ferrone et al. (Ferrone, F. A., J. Hofrichter, H. Sunshine, and W. A. Eaton. 1980. Biophys. J. 32:361-377; Ferrone, F. A., J. Hofrichter, and W. A. Eaton. 1985. J. Mol. Biol. 183:611-631) to describe the spatial dependence of the radial growth of polymer domains of sickle hemoglobin. Although this extended model requires the consideration of effects such as monomer diffusion, which are irrelevant to a spatially uniform description, no new adjustable parameters are required because diffusion constants are known independently. We find that monomer diffusion into the growing domain can keep the net unpolymerized monomer concentration approximately constant, and in that limit we present an analytic solution of the model. The model shows the features reported by Basak, S., F. A. Ferrone, and J. T. Wang (1988. Biophys J. 54:829-843) and provides a new means of determining the rate of polymer growth. When spatially integrated, the model exhibits the exponential growth seen in previous studies, although molecular parameters derived from analysis of the kinetics assuming uniformity must be modified in some cases to account for the spatially nonuniform growth. The model developed here can be easily adapted to any spatially dependent polymerization process.

Hemoglobin, Sickle↗
PubMed1987

Polymer domains, gelation models and sickle cell crises.

The multistranded fibers formed by deoxygenated sickle hemoglobin form well ordered spherulitic arrays called domains. Employing laser photolysis of the carboxy derivative to initiate polymerization and domain formation, we have monitored the evolution of the spatial character of domains by light scattering and birefringence. Spatial growth is analyzed by observing a 62.5 microns square area of the sample and storing the image as 2500 discrete elements. Domain formation appears to consist of two phases. In the early phase even symmetric domains are not radially isotropic. Although the domain expands during this period, the internal polymer density as inferred by the light scattering intensity also increases. In the second phase, the domain becomes structurally symmetric and spatially homogeneous, and changes in the scattered intensity including pronounced overshoots occur uniformly across the monitored region. In this phase, the birefringence increases as the scattering decreases, with the same apparent rate.

Birefringence↗
PubMedDate not supplied

Cystic echinococcosis in semi-nomadic pastoral communities in north-west China.

In order to determine the prevalence of human cystic echinococcosis (CE) in semi-nomadic traditional pastoralist groups in north-west China, 2 large community studies were undertaken in Altai and Tacheng Prefectures in 1990/91 and 1995/96, respectively. The Kekergash community (Altai) comprised mainly ethnic Kazakhs, whereas the Narenhebuke community (Tacheng) comprised mainly Mongolians. Populations were screened for CE by abdominal ultrasound scan (US) and serological tests. The total prevalence of confirmed human CE was higher in Narenhebuke (2.7%, 49/1844) than in Kekergash (0.9%, 17/1861; P < 0.01). Within each community there was no significant difference of CE prevalence between the Kazakh and Mongolian groups, although Han Chinese exhibited twice the rate of CE (4.9%) in Narenhebuke compared to the dominant Mongolian population. For each community, human CE prevalence increased with age and there was a greater risk associated with the practice of home slaughter of livestock. Dogs were screened for Echinococcus granulosus infection and re-infection levels using a highly specific coproantigen test. The proportion of dogs with positive coproantigen tests was significantly higher in Narenhebuke (36.0%, 50/139) compared to Kekergash (17.8%, 16/90). In Narenhebuke the re-infection levels of dogs, as determined by coproantigen positivity, were higher in the winter quarters (49.4%, 39/79) compared to the summer quarters (18.3%, 11/60; P < 0.01). Furthermore, coproantigen re-test positivity was 25% at 3 months and 29.2% at 7 months. Highest dog coproantigen positivity was obtained over the winter period.

Adolescent↗