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F Morán

Publications and source records attributed to F Morán.

At least 19 recordsLinked to original sources
PubMed2001

SOMCD: method for evaluating protein secondary structure from UV circular dichroism spectra.

This article presents SOMCD, an improved method for the evaluation of protein secondary structure from circular dichroism spectra, based on Kohonen's self-organizing maps (SOM). Protein circular dichroism (CD) spectra are used to train a SOM, which arranges the spectra on a two-dimensional map. Location in the map reflects the secondary structure composition of a protein. With SOMCD, the prediction of beta-turn has been included. The number of spectra in the training set has been increased, and it now includes 39 protein spectra and 6 reference spectra. Finally, SOM parameters have been chosen to minimize distortion and make the network produce clusters with known properties. Estimation results show improvements compared with the previous version, K2D, which, in addition, estimated only three secondary structure components; the accuracy of the method is more uniform over the different secondary structures.

Algorithms↗
PubMed2001

Simulation of plasticity in the adult visual cortex.

Retinal plasticity has been shown in the adult visual nervous system in mammals. Following a retinal lesion (scotoma) there is a reorganization of the cortical receptive field distribution: cortical neurons selective to visual stimuli in the area of the visual field corresponding to the retinal lesion, become selective to other parts of the visual field. In this work, we study this effect with a self-organizing neural network. In a first stage, the network reaches a pattern of connectivity that represents normal development of neuronal selectivity. The scotoma is simulated by perturbing accordingly the properties of a region of the input layer representing the retina. The system evolves to a new receptive field distribution mainly by means of the reorganization of the intra cortical connectivity. No major change of the geniculo cortical connectivity is detected. This may explain the surprisingly short time scale of the event.

Age Factors↗
PubMed2000

Reconstruction of protein form with X-ray solution scattering and a genetic algorithm.

We have reconstructed, from experimental approximately 2 nm resolution X-ray solution scattering profiles, the corresponding shapes and sizes of myoglobin, troponin C, spermadhesin PSP-I/PSP-II, chymotrypsinogen A, superoxide dismutase, ovalbumin, tubulin, nitrite reductase, catalase, the structural change of troponin C upon dissociation of the two high affinity Ca(2+), and the solution model structure of a tandem pair of fibronectin type III cytoplasmic domains of integrin alpha6beta4 before determination of its crystal structure. To this purpose we have designed a new genetic algorithm which gradually explores a discrete search space and evolves convergent models made of several hundred beads (down to 0.3 nm radius) best fitting the scattering profile upon Debye calculation, without geometrical constraints or penalty for loose beads. This is a procedure of effective numerical transformation of the one-dimensional scattering profiles into three-dimensional model structures. The number of beads in models is correlated with the protein molecular mass (with one exception). The shape and approximate dimensions of each protein have been retrieved by a set of ten solution models, essentially superimposable with the available crystal structures.

Algorithms↗
PubMed1998

Coexistence of multiple propagating wave-fronts in a regulated enzyme reaction model: link with birhythmicity and multi-threshold excitability.

We analyze the spatial propagation of wave-fronts in a biochemical model for a product-activated enzyme reaction with non-linear recycling of product into substrate. This model was previously studied as a prototype for the coexistence of two distinct types of periodic oscillations (birhythmicity). The system is initially in a stable steady state characterized by the property of multi-threshold excitability, by which it is capable of amplifying in a pulsatory manner perturbations exceeding two distinct thresholds. In such conditions, when the effect of diffusion is taken into account, two distinct wave-fronts are shown to propagate in space, with distinct amplitudes and velocities, for the same set of parameter values, depending on the magnitude of the initial perturbation. Such a multiplicity of propagating wave-fronts represents a new type of coexistence of multiple modes of dynamic behavior, besides the coexistence involving, under spatially homogeneous conditions, multiple steady states, multiple periodic regimes, or a combination of steady and periodic regimes.

Journal Article↗
PubMed1998

Low-resolution structures of proteins in solution retrieved from X-ray scattering with a genetic algorithm.

Small-angle x-ray solution scattering (SAXS) is analyzed with a new method to retrieve convergent model structures that fit the scattering profiles. An arbitrary hexagonal packing of several hundred beads containing the problem object is defined. Instead of attempting to compute the Debye formula for all of the possible mass distributions, a genetic algorithm is employed that efficiently searches the configurational space and evolves best-fit bead models. Models from different runs of the algorithm have similar or identical structures. The modeling resolution is increased by reducing the bead radius together with the search space in successive cycles of refinement. The method has been tested with protein SAXS (0.001 < S < 0.06 A(-1)) calculated from x-ray crystal structures, adding noise to the profiles. The models obtained closely approach the volumes and radii of gyration of the known structures, and faithfully reproduce the dimensions and shape of each of them. This includes finding the active site cavity of lysozyme, the bilobed structure of gamma-crystallin, two domains connected by a stalk in betab2-crystallin, and the horseshoe shape of pancreatic ribonuclease inhibitor. The low-resolution solution structure of lysozyme has been directly modeled from its experimental SAXS profile (0.003 < S < 0.03 A(-1)). The model describes lysozyme size and shape to the resolution of the measurement. The method may be applied to other proteins, to the analysis of domain movements, to the comparison of solution and crystal structures, as well as to large macromolecular assemblies.

Algorithms↗
PubMed1996

Structural study of the development of ocularity domains using a neural network model.

We present a model for the development of ocularity domains in the visual cortex of mammals during the embryonic stage. We model the thalamo-cortical pathway with a self-organising neural network with two source layers, each of them serving different retinae, and one target layer, where the connections end. The connectivity between the source layers and the target layer is driven by Hebbian learning. In both the source layers and the target layer we assume excitatory lateral signal diffusion between proximal neurons that causes them to be correlated. According to the developmental state being modelled, we do not consider either correlation or anti-correlation between the signals originated in neurons of different retinae. The basic assumptions made are proved to be sufficient to attain a distribution of connections arranged in ocularity domains. The dependence of the geometry of the ocularity domains on the parameters of the model is analysed and a correlation between the width of the signal diffusion and the extent of the domains is found. The generality of the assumptions made allows an easy translation of the model to explain the development of other elements of the sensory nervous system.

Animals↗
PubMed1993

Circular dichroism analysis of ligand-induced conformational changes in protein kinase C. Mechanism of translocation of the enzyme from the cytosol to the membranes and its implications.

The structural changes following the binding to protein kinase C (PKC) of activators that promote its translocation to lipid environments were studied by far-u.v. c.d. and intrinsic fluorescence measurements of the protein. In the absence of activators, PKC contained 40% alpha-helix, with an average size of 13 amino acids per alpha-helix segment, and 12% beta-structure as deduced from c.d. spectral analysis while fitting a set of model proteins of known structure. Ligands that promote translocation and activation of the enzyme, such as Ca2+ ions and phorbol esters, produced drastic changes in the c.d. spectra which may be interpreted as a reduction in the average number of consecutive amino acids in the alpha-helix. Most of the total alpha-helix structure was conserved and an increase in beta-structure was produced by active phorbol esters. These activators differentially affected the fluorescence of PKC: phorbol esters shifted the emission maximum to the red, whereas Ca2+ produced a marked decrease in the intensity of the fluorescence emission, suggesting in both cases that tryptophan residues were exposed to increased polar environments after binding of the ligands.

Animals↗
PubMed1993

Evaluation of secondary structure of proteins from UV circular dichroism spectra using an unsupervised learning neural network.

An optimized self-organizing map algorithm has been used to obtain protein topological (proteinotopic) maps. A neural network is able to arrange a set of proteins depending on their ultraviolet circular dichroism spectra in a completely unsupervised learning process. Analysis of the proteinotopic map reveals that the network extracts the main secondary structure features even with the small number of examples used. Some methods to use the proteinotopic map for protein secondary structure prediction are tested showing a good performance in the 200-240 nm wavelength range that is likely to increase as new protein structures are known.

Algorithms↗
PubMed1991

Cooperative interaction of the C-terminal domain of histone H1 with DNA.

We have studied the interaction of the isolated C-terminal domain of histone H1 with linear DNA using precipitation curves and electron microscopy. The C-terminal domain shows a salt-dependent transition towards cooperative binding, which reaches completion at 60 mM NaCl. At this salt concentration, the C-terminal domain binds to some of the DNA molecules, leaving the rest free. A binding site of 22 base-pairs can be calculated from the stoichiometry of the precipitated fractions. The C-terminal domain condenses the DNA in toroidal particles. The average inner radius of the particles is of the order of 195 A. Consideration of the value of the inner radius of the toroids in the light of counterion condensation theory suggests that in these complexes the isolated C-terminal domain is capable of nearly full electrostatic neutralization of the DNA phosphate charge.

Animals↗
PubMed1991

PASHEMOS: a versatile program written in Pascal to simulate patterns on the shells of molluscs, according to the Meinhardt model.

In this paper we describe PASHEMOS, a user-friendly program written in Pascal to solve the Meinhardt-Klingler model numerically. This model studies the shell pattern pigmentation of molluscs. Moreover, PASHEMOS enables theoretical analysis to be performed on the different steady states. The program takes into account the four differential equation systems established in the model. It numerically solves these systems. This program is developed in such a way that both the equation system type and the parameter values can be chosen. The pattern is displayed in each case, and other output possibilities are available (i.e. three-dimensional concentration plotting, phase plane, phase space, stability analysis). The implementation of the program for the case of a three-variable system is shown as an example of PASHEMOS handling. Program applications for other models are also discussed.

Algorithms↗
PubMed1989

Kinetic analysis of psi-DNA structure formation induced by histone H1 and its C-terminal domain.

In this paper we have studied the kinetics of psi-DNA structure formation induced by H1 and H1 peptides containing the C-terminal domain, namely the CTB peptide, obtained by thrombin digestion, and the CNBS peptide, derived from N-bromosuccinimide treatment of H1. The time course for the formation of the psi structure has been followed by measuring the changes in ellipticity at 270 nm as a function of time under different experimental conditions. In all cases studied here, we have observed the existence of two elementary processes: one fast, the other slow. Kinetic experiments performed with high molecular weight DNA showed that the greater the salt concentration, the higher was the apparent rate of psi structure formation. In complexes formed with sonicated DNA and H1, CNBS and CTB, we observed that the greater the content of the C-terminal domain, the higher was the apparent rate at which the final psi structure was reached. Thus, the presence of increasing amounts of either salt or C-terminal domain facilitates the formation of the psi structure. The molecular basis for these phenomena is discussed. The influence of the order of addition of the different components of the complex on the kinetics of psi structure induction is also studied.

Circular Dichroism↗
PubMed1988

A BASIC microcomputer program to calculate the secondary structure of proteins from their circular dichroism spectrum.

A BASIC program (CDPROT) has been developed to calculate the secondary structure of proteins from their far UV circular dichroism spectrum. This implementation can use different reference spectra, calculated either from model polypeptides or proteins of known tertiary structure. Apart from obtaining the alpha-helical, beta-structure, beta-turns or random percentages which would generate the spectrum of best fit with respect to the experimental measures, CDPROT represents on screen both theoretical and experimental spectra indicating the root-mean-square error. The provision of additional reference spectra by the user is also considered, and another program (STOREREF) performs the editing in an adequate format for CDPROT.

Algorithms↗
PubMed1987

Studies on evolutionary and selective properties of hypercycles using a Monte Carlo method.

The most relevant properties of hypercycles were previously studied mainly from a theoretical point of view. We have developed a Monte Carlo method simulating hypercyclic organization to obtain information about the dynamics of this prebiotic organization. Nucleation, growth, and selective properties have been tested and the results obtained are in good agreement with those of the theoretical predictions. The influence of hypercyclic organization on the "error threshold" has also been studied. As a consequence of the emergence of a hypercycle, the value of this threshold decreases. The amount of this decrease depends on the population size. Moreover, for some interval of quality factor values, either the hypercycle organization or an error catastrophe can be produced, depending on the initial conditions. The influence of these phenomena on both the dynamic behavior and evolutionary advantages of the hypercycle, as well as their decisive roles on genome size, are discussed.

Biological Evolution↗
PubMed1985

Condensation of DNA by the C-terminal domain of histone H1. A circular dichroism study.

The condensation of DNA by the C-terminal domain of histone H1 has been studied by circular dichroism in physiological salt concentration (0.14 M NaF). As the intact H1 molecule, its C-terminal domain induces the so-called psi state of DNA that is characterized by a nonconservative circular dichroism spectrum which is currently attributed to ordered aggregation of the DNA molecules. On a molar basis, intact H1 and its C-terminal domain give spectra of similar intensity. Neither the globular domain of H1 nor an N-terminal fragment, that includes both the globular and N-terminal domains, has any effect on the conservative circular dichroism of DNA. From these results it is concluded that the condensation of DNA mediated by histone H1 is mainly due to its C-terminal domain. The effect of the salt concentration and the size of DNA molecules on the circular dichroism of the complexes are also examined.

Animals↗
PubMed1985

Kinetics of conformational changes in the globular head of calf thymus H1 upon tryptic digestion.

The influence of the N- and C-terminal tails on the conformation of the globular domain of histone H1 from calf thymus has been investigated by monitoring the changes in absorption far UV circular dichroism and fluorescence spectra due to the tryptic digestion of the molecule. The values of kinetic constants obtained for the time course of the reaction followed by different above mentioned techniques seem to indicate that whereas the relaxation in the tyrosine environment occurs due to the digestion of the polar tails, the alpha-helix content increases in the earlier phase of the digestion.

Animals↗
PubMed1984

Onset of birhythmicity in a regulated biochemical system.

We analyze the onset of multiple oscillatory regimes in a two-variable biochemical model previously proposed for glycolytic oscillations. The model, based on the activation of an allosteric enzyme by a reaction product, is modified by introduction of recycling of product into the substrate. This modification creates the conditions for birhythmicity in which two stable oscillatory regimes coexist under the same conditions. The detailed route by which birhythmicity develops from a single oscillatory regime is elucidated by means of bifurcation diagrams. It is shown that birhythmicity provides added sensitivity to the oscillatory system as the same type of perturbation may produce a switch from one periodic regime to the other and back, when applied at the appropriate phase of each of the two oscillations.

Animals↗
PubMed1980

Structural studies on histones H1. Circular dichroism and difference spectroscopy of the histones H1 and their trypsin-resistant cores from calf thymus and from the fruit fly Ceratitis capitata.

A peptide containing the globular region of the histone H1 from the fruit fly Ceratitis capitata has been isolated after limited tryptic digestion of insect H1. The composition of this trypsin-resistant core resembles that of the homologous peptide from calf thymus H1, although the insect H1 core possesses one cysteine, two tyrosines, one histidine, and more isoleucine and less glycine and leucine than the calf thymus H1 core. Circular dichroism measurements indicate that all the fragments that possess an ordered secondary structure (approximately 11% in both calf thymus H1 and Ceratitis H1) are present in the trypsin-resistant cores. Both calf thymus and Ceratitis H1 and their trypsin-resistant cores fold cooperatively on titration with NaOH, though the folding of the cores is less cooperative than that for the parentmolecules. On the other hand, salt-induced folding of both cores and intact molecules is noncooperative. The environment of the tyrosyl residues in both calf thymus and Ceratitis H1 has been studied by circular dichroism in the region 250-300 nm and by difference spectroscopy; their pKa' values have also been determined. The results suggest that one of the tyrosyl residues of Ceratitis H1 is buried in the hydrophobic core, in an environment similar to that of calf thymus tyrosine-72, while the second tyrosyl residue of the insect H1 molecule, which titrates with a lower pKa' value (approximately 9.30 in the absence of salt and approximately 9.80 in the presence of 0.3 M KF), is on the surface of the trypsin-resistant core. Due to the limited number of aromatic residues in the histone molecules, the above-mentioned techniques proved to be useful tools to study conformational transitions.

Amino Acids↗