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D Poland

Publications and source records attributed to D Poland.

At least 19 recordsLinked to original sources
PubMed2001

Maximum-entropy determination of self-association distribution functions; daunorubicin and ATP.

In the present paper we show how one can use the perturbation of some molecular optical property (for example circular dichroism or chemical shift) as a function of concentration to construct cluster distribution functions describing the self-association of molecules in solution. The optical data are first converted into data giving the variation of the average extent of clustering as a function of the total concentration and then, using straightforward thermodynamics, a set of moments of the cluster distribution function can be obtained. Utilizing the maximum-entropy method, the moments are then used to calculate approximate distribution functions, where the more moments that are used the better the approximation obtained. Given the probability distribution for clusters of different sizes one can then calculate the equilibrium constant for each stage of association. Thus one converts average degree of association into equilibrium constants without having to use any specific model. By this method one can clearly tell whether the equilibrium constants remain constant, increase, or decrease with the number of molecules in a cluster. We apply the method to literature data for two systems, namely daunorubicin, which has a strong tendency to cluster in solution, and Mg(ATP)(2-) which forms weaker clusters. We find that the successive equilibrium constants for adding a monomer to a cluster are approximately constant for daunorubicin but clearly decrease as a function of increasing cluster size for Mg(ATP)(2-).

Adenosine Triphosphate↗
PubMed2001

Free energy distributions in proteins.

Protein molecules in solution have a broad distribution of enthalpy states. A good approximation to the distribution function for enthalpy states can be calculated, using the maximum-entropy method, from the moments of the distribution that, in turn, are obtained from the experimental temperature dependence of the heat capacity. In the present paper, we show that the enthalpy probability distribution can then be formulated in terms of a free energy function that gives the free energy of the protein corresponding to a particular value of the enthalpy. By the location of the minima in this function, the free energy distribution graphically indicates the most probable values of the enthalpy for the protein. We find that the behavior of the free energy functions for proteins falls somewhere between two different cases: a two-state like function with two minima, the relative levels of the two states changing with temperature; and, a single-minimum function where the position of the minimum shifts to higher enthalpy values as the temperature is increased. We show that the temperature dependence of the free energy function can be expressed in terms of a central free energy distribution for a given, fixed temperature (which is most conveniently chosen as the temperature of the maximum in the heat capacity). The nature of this central free energy function for a given protein thus yields all of the thermodynamic behavior of that protein over the temperature range of the denaturation process.

Bacterial Proteins↗
PubMed2001

Ligand binding distributions in nucleic acids.

We illustrate a new method for the determination of the complete binding polynomial for nucleic acids based on experimental titration data with respect to ligand concentration. From the binding polynomial, one can then calculate the distribution function for the number of ligands bound at any ligand concentration. The method is based on the use of a finite set of moments of the binding distribution function, which are obtained from the titration curve. Using the maximum-entropy method, the moments are then used to construct good approximations to the binding distribution function. Given the distribution functions at different ligand concentrations, one can calculate all of the coefficients in the binding polynomial no matter how many binding sites a molecule has. Knowledge of the complete binding polynomial in turn yields the thermodynamics of binding. This method gives all of the information that can be obtained from binding isotherms without the assumption of any specific molecular model for the nature of the binding. Examples are given for the binding of Mn(2+) and Mg(2+) to t-RNA and for the binding of Mg(2+) and I(6) to poly-C using literature data.

Binding Sites↗
PubMed2001

Increased alpha3-fucosylation of alpha(1)-acid glycoprotein in patients with congenital disorder of glycosylation type IA (CDG-Ia).

Increased fucosylation of the type (sialyl) Lewis(x) was detected on the acute-phase plasma protein alpha(1)-acid glycoprotein (AGP) in patients with the congenital disorder of glycosylation type IA. This is remarkable, because in these patients the biosynthesis of guanosine 5'-diphosphate (GDP)-D-mannose is strongly decreased, and GDP-D-mannose is the direct precursor for GDP-L-fucose, the substrate for fucosyltransferases. The concomitantly occurring increased branching of the glycans of AGP and the increased fucosyltransferase activity in plasma suggest that a chronic hepatic inflammatory reaction has induced the increase in fucosylation.

Amidohydrolases↗
PubMed2001

Enthalpy distribution for the alpha-helix/random coil transition in a model peptide: a study of two-state behavior.

We use heat capacity data of Taylor et al. to calculate the enthalpy distribution of a model peptide using the moments/maximum-entropy method. The peptide was designed with small covalent loops at both ends of the molecule to nucleate alpha-helix thus giving a system that would be expected to show a helix-coil transition that is very close to being two state. If we subtract a background contribution from the heat capacity data, then the enthalpy distribution we obtain shows two distinct peaks representing helix and coil. The difference in the peak enthalpy values agrees closely with the DeltaH obtained from the two-state analysis. On the other hand, if we use the complete heat capacity without subtracting background we then obtain an enthalpy distribution that has only a single peak at all temperatures. We show that this result can be consistent with the existence of two states, helix and coil, but only if the range of variation of the enthalpy of each species is so large as to make the notion of a species fairly meaningless.

Amino Acid Sequence↗
PubMed2001

Enthalpy distributions in proteins.

Experimental data on the temperature dependence of the heat capacity of proteins can be used to calculate approximate enthalpy distributions for these molecules using the maximum-entropy method. C(p) (T) data is first used to calculate a set of moments of the enthalpy distribution, and these are then used to estimate the enthalpy distribution. If one knows the temperature expansion of the heat capacity through the (n - 2)th power of DeltaT (measured from the expansion center), then this is enough information to calculate the nth moment of the enthalpy distribution. Using four or more moments is in turn enough information to resolve bimodal behavior in the distribution. If the enthalpy distribution of a protein exhibits two distinct peaks, then this is direct experimental confirmation of a two-state mechanism of denaturation, the two peaks corresponding to the enthalpy of the native and unfolded species respectively. If the heat capacity of a protein exhibits a maximum at the denaturation temperature, then there is the possibility that the enthalpy distribution will be bimodal, but the presence of a maximum in the heat capacity is not a sufficient condition for this kind of behavior. We construct a phase diagram in terms of the appropriate variables to indicate when a maximum in the heat capacity will also give rise to bimodal behavior in the enthalpy distribution. We illustrate the phase diagram using literature data for a set of proteins.

Calorimetry↗
PubMed2001

Protein-binding polynomials.

Using a new method recently published for analyzing the binding isotherms of biopolymers (Poland, 2000a), we calculate the complete binding polynomials for lysozyme, insulin, and serum albumin from published titration data. These three proteins have, respectively, 22, 32, and 184 dissociable protons and hence are represented by series in powers of the hydrogen ion concentration with the highest powers in the series being the numbers just indicated. Given the complete binding polynomial, the distribution function giving the concentration of all states of proton binding can then be calculated at any pH.

Hydrogen-Ion Concentration↗
PubMed1999

Defects in associating systems: example of actin.

A statistical mechanical model is given for linear associating systems that contain defects, using the double-stranded actin polymer as an example. We treat the system as a one-dimensional lattice that can desorb monomers (giving defects) using grand partition function techniques. The main difference from a standard adsorption problem is that the monomer units are also responsible for the structural integrity of the lattice (polymer) and if too many desorb the polymer will be broken. We use literature data to estimate the density of defects in the actin polymer.

Actins↗
PubMed1998

A follow-up study for estimating the effectiveness of a cross-gender hormone substitution therapy on transsexual patients.

This follow-up study was carried out to validate the effectiveness of cross-gender hormone therapy embedded in a multistep treatment concept for transsexual patients. This therapy described in detail by the authors elsewhere and presented briefly below provides cross-gender hormone substitution to obtain an assimilation of secondary sex characteristics to the desired sex as quickly as possible. Personal and social background data of 46 male-to-female (M-to-F) and 42 female-to-male (F-to-M) patients passing through different stages of the treatment concept were included. In the Endocrinological Outpatient Clinic of the Max-Planck-Institute/Munich the effectiveness of cross-gender hormone replacement therapy as well as frequency and distribution of side effects were examined by follow-up examination of endocrinological parameters. Cross-gender hormones were administered either parenterally or orally. Blood samples were collected routinely after 2 to 6 months depending on the duration of hormone substitution and complication rate. The incidence of hyperprolactinemia in estrogen-treated M-to-F transsexuals lies in the range of studies published before, whereas the number of patients developing galactorrhea is significantly lower in our patients. The incidence of thromboembolic events during the time of cross-gender hormone treatment in our patients is negligible. Changes in hematological parameters are observed under cross-gender hormone therapy. With the cross-gender hormone regimen performed by us it is possible to generate less side effects in the treatment of transsexual patients than described before.

Female↗
PubMed1997

Membrane association of FtsY, the E. coli SRP receptor.

FtsY, the Escherichia coli homologue of the eukaryotic SRP receptor (SR alpha), is located both in the cytoplasm and in the inner membrane of E. coli. Similar to SR alpha, FtsY consists of two major domains: a strongly acidic N-terminal domain (A) and a C-terminal GTP binding domain (NG) of which the crystal structure has recently been determined. The domains were expressed both in vivo and in vitro to examine their subcellular localization. The results suggest that both domains associate with the membrane but that the nature of the association differs.

Bacterial Proteins↗
PubMed1988

Accuracy and precision of the Tono-Pen in measuring intraocular pressure after keratoplasty and epikeratophakia and in scarred corneas.

Intraocular pressure measurements with the Goldmann and Schiotz tonometers are unreliable when the cornea is irregular due to disease or surgery. The Tono-Pen (Oculab, Glendale, Calif) is an electronic applanation tonometer based on the same principle as the MacKay-Marg tonometer. We measured intraocular pressure in 37 eyes with irregular corneas, in 50 eyes that had recently undergone penetrating keratoplasty, in 16 eyes that had undergone epikeratophakia, and in 12 eyes with normal corneas with both the MacKay-Marg and Tono-Pen tonometers. The same two instruments were used, and the sequence of measurement was randomized. Analysis of variance demonstrated no significant difference between measurements obtained with the two tonometers in any of the groups. The data suggest that the Tono-Pen is as accurate as the MacKay-Marg tonometer in those situations where the Goldmann tonometer is inaccurate.

Cicatrix↗