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Biomedical subjects

B Maigret

Publications and source records attributed to B Maigret.

At least 55 records · Page 3Linked to original sources
PubMed1992

Computer simulation of the conformational behaviour of angiotensinogen (6-13) renin substrate.

The conformational behaviour of the biologically active angiotensinogen (6-13) fragment has been investigated by computer simulations. A large sample of conformers has been generated using the Monte-Carlo procedure, then analysed using classification and partition methods. Seven families can describe the conformational distribution. About 40% of conformers are fully extended, 28% are folded at the C-terminal His6-Pro7-Phe8-His9 level and the others are folded at different levels. The study highlights the extreme flexibility of the angiotensinogen fragment.

Amino Acid Sequence↗
PubMed1992

Computational simulations of the conformational behaviour of the adhesive proteins RGDS fragment.

Many adhesive proteins present in extracellular matrices and in blood contain the tetrapeptide sequence -Arg-Gly-Asp-Ser- (or RGDS) at their cell recognition site. Since this sequence, or similar ones, was found in many proteins involved in major biological mechanisms, conformational investigations were performed on the RGDS fragment. A preliminary review of available crystal structures indicates that the RxDy sequences exhibit 3 well-defined structural patterns: one corresponding to a strong interaction between the Arg and Asp ionic side chains which are only about 4 A apart, one with the ions separated by about 8 A, and another in which the side chains are further apart (about 11 A). The conformational behaviour of the isolated RGDS fragment was next tackled using sequential building, Monte Carlo and molecular dynamics computational techniques. Analysis of the RGDS sequence conformational possibilities, as simulated in vacuum and in water solution, indicates that they can be classified into several conformational classes, which correspond roughly to the behaviour of the RGDS fragment as observed in protein matrices. This suggests the possibility of understanding the biological role of the RGDS or parent sequences in recognition processes.

Amino Acid Sequence↗
PubMed1992

MOL3D--a modular and interactive program for molecular modeling and conformational analysis: II. Extended modules.

The new release of MOL3D, a molecular modeling program written in FORTRAN, contains not only enhanced graphic capabilities, but also an improved module for intermolecular calculations that allows rigid and flexible docking. Various interfaces have been added to some well-known and widely diffused programs, such as MM2, AMBER and MOPAC, and to the Cambridge Crystallographic Database. Finally a graph manager and a samples database have been added, which allow efficient searches with various requirements concerning structural templates, pharmacophoric three-dimensional (3D) constraints, and the field of biological activity, if any.

Computer Graphics↗
PubMed1991

Program for the visualization of inorganic crystals.

A program has been developed to manipulate images of inorganic structures and organic molecules on ALLIANT VFX/40 using the PHIGS + standard. This article reviews algorithms for representing spheres, ellipsoids and various polyhedrons involved in inorganic chemistry. The program also supports the display and manipulation of animated frames from dynamics simulations. Many graphical facilities have been implemented and we discuss their interest in the field of molecular graphics.

Algorithms↗
PubMed1991

Computational analysis of conformational behavior of cholecystokinin fragments. I-CCK4, CCK5, CCK6 and CCK7 molecules.

A conformational analysis has been performed on several peptide fragments (CCK4 to CCK7) of the cholecystokinin neuromodulator. The Monte-Carlo Metropolis method was used to explore the conformational space of all these flexible units and different electric charge distributions were introduced in order to mimic pH effects. Results agree reasonably well with experimental data from NMR and fluorescence experiments. The CCK4 fragment displays a peculiar conformational behavior when compared to all other longer peptides with short range interaction between the Trp and Phe aromatic side-chains. Several H-bonded conformers including C- or beta-turns are found for CCK5 to CCK7. These findings are correlated to the central and peripheral actions of these compounds and hypotheses concerning the best possible templates for each one are discussed.

Amino Acid Sequence↗
PubMed1990

New determinations and simplified representations of macromolecular surfaces.

Several new methods or improvements of older algorithms determining the different pieces of molecular surface are presented. Their improvement in time and their complexity are discussed. Only the indexes of the atoms on which the pieces are relying are, in fact, determined, since their explicit representation from these numbers varies according to the 3D capabilities of the graphic workstation (dots, grid, etc.), and this generation is not C.P.U. consuming. To have a simplified representation of the surface of macromolecules, a polyhedron with planar triangular faces is then introduced: Each concave triangular surface piece is replaced with planar triangles relying on its three atomic centers, while saddle-shaped rectangles and convex pieces are wholly ignored. A minimal data structure of the polyhedron is then proposed, which contains only topological informations, since no coordinates have been generated. If the atomic radius is then considered to be constant (independent of atomic type), the surface of a set of N points is now defined by the choice of a subset with a topology. This choice is controlled by a parameter of rugosity (the atomic radius). Contrary to Voronoi polyhedrons partition, which gives a topology for a set of N points, our approach gives a topology only for the exterior points of this set. A few applications of this very simple definition of molecular surface are then discussed: the 3D interactive manipulation of macromolecules, the steric intermolecular recognition, and the determination of local and global properties of the surface.

Computer Graphics↗
PubMed1989

Delta opioid receptor selectivity induced by conformational constraints in linear enkephalin-related peptides: 1H 400-MHz NMR study and theoretical calculations.

Introduction into the structure of the linear hexapeptide DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr) or DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr) of tert-butyl groups as constraints different from cyclization leads to a large increase in the selectivity for delta opioid binding site in the case of DSTBULET [Tyr-D-Ser-(OtBu)-Gly-Phe-Leu-Thr] (Ki delta = 6.14 nM; Ki mu = 374 nM) and BUBU [Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu)] (Ki delta = 4.68 nM; Ki mu = 475 nM) or a loss of affinity for DTTBULET [Tyr-D-Thr(OtBu)-Gly-Phe-Leu-Thr] (Ki delta = 866 nM; Ki mu = 4500 nM). This puzzling behavior is studied here by 400-MHz 1H NMR spectroscopy in DMSO-d6 solution and by theoretical calculations. When DSLET and DTLET are compared, the reduction in energetically accessible phi and psi angles induced by the tert-butyl group in the D-Ser2 residue decreases the degree of freedom in the N-terminal part of the peptides. For DSTBULET and BUBU, the rigidification of the backbone evidenced by the appearance of the large NOE's of Phe4 NH-Gly3 alpha and Gly3 NH-alpha and by the loss of the C7 folding around the D-Ser2 residue found in DSLET could explain the drastic loss of affinity for mu opioid receptors. In DTTBULET, a large change in the spatial orientation around the D-Thr2 (OtBu) residue forces the aromatic rings far from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Computer simulation of the conformational behavior of cholecystokinin fragments: conformational families of sulfated CCK8.

Display methods, such as principal component analysis, and clustering methods were applied to a sample of cholecystokinin, (sulfated CCK8) conformations obtained from a Monte Carlo simulation. It is shown that six families of conformations can entirely describe the sample. Each family represents a typical conformer. These theoretical models are in agreement with recent experimental results which stress the predominance of folded conformers in aqueous medium.

Computer Simulation↗
PubMed1986

Conformational analysis of cholecystokinin CCK26-33 and related fragments by 1H NMR spectroscopy, fluorescence-transfer measurements, and calculations.

The conformational behavior of CCK7, Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2, and CCK8, Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH2, in their sulfated and unsulfated forms, was studied both by 1H NMR spectroscopy in dimethyl-d6 sulfoxide and water and by fluorescence-transfer measurements at pH 7. In neutral conditions, both experimental methods show that these peptides exist preferentially in folded forms with beta and gamma turns around the sequence Gly-Trp-Met-Asp and Met-Asp-Phe-NH2, respectively. The presence of stable folded conformations is supported by through-space effects during the titration of the ionizable groups and by the weak temperature dependency of some amide protons not only in dimethyl sulfoxide but also in water. The folding of the C-terminal part, already shown in CCK5, seems to be a common conformational characteristic in CCK peptides. The N-terminal part of CCK8 presents an equilibrium between beta and gamma turns, whereas this part of the peptide is more flexible in CCK7. The low quantum yield of Tyr and the large mean distance (R = 15 A) between Tyr and Trp, determined by fluorescence-transfer measurements, support the occurrence of folded conformations pushing the aromatic rings far from each other. Interestingly, the introduction of the sulfate group enhances the folding tendency even in aqueous medium. The larger amide temperature dependency and the decrease in the R distance at acidic pH suggest that an intramolecular ionic interaction involving the N-terminal amino group and the beta-carboxyl groups of Asp32 stabilize the folded forms. Metropolis calculations performed on CCK8 support the existence of stable folded conformations closely related to those deduced from experimental data.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1986

Proposals for the mu-active conformation of the enkephalin analog Tyr-cyclol(-N gamma-D-A2-bu-Gly-Phe-Leu-).

The conformational behavior of the sterically restricted cyclic peptide Tyr-cyclo(-N gamma-D-A2-bu-Gly-Phe-Leu-), proposed recently as an enkephalin analog with high opiate activity, is examined by theoretical investigations. The method used allows the search of conformational energy minima associated with cyclic structures fitting a hypothetical opiate pharmacophore. The results obtained show that, despite the fact that many cyclic structures of low conformational energy can be found for this compound, only one of them can be retained as a conformer presenting the characteristic features of the imposed pharmacophore. This conformation is stabilized by an intramolecular H-bond between the D-A2bu-carbonyl and the Leu NH group so that a beta-turn is formed. This structure also presents a high mobility of the Tyr1 side-chain which can fit the tyramine moiety of rigid opiates with minor loss of conformational energy. A two-step binding mechanism is proposed for the interactions of this cyclic peptide with its receptor which could be an intermediate between the "zipper" model proposed for flexible linear peptides and the "lock-and-key" model adapted to rigid molecules. The selectivity of enkephalin analogs for mu and delta opioid receptors is discussed in light of the present theoretical investigations.

Enkephalin, Leucine↗
PubMed1983

Models for the conformational behaviour of angiotensin-II in acidic aqueous solutions.

Clustering analysis is applied to a sample of Angiotensin-II conformations obtained from a Monte-Carlo procedure. It is shown that 5 families of conformations can describe entirely the sample. Each family can be represented by a typical conformer. Two of these last models are predominant in the description of Angiotensin-II in acidic solutions. These theoretical models are in agreement with recent experimental results.

Angiotensin II↗