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C Etchebest

Publications and source records attributed to C Etchebest.

At least 19 recordsLinked to original sources
PubMed2006

Protein Peeling 2: a web server to convert protein structures into series of protein units.

Protein Peeling 2 (PP2) is a web server for the automatic identification of protein units (PUs) given the 3D coordinates of a protein. PUs are an intermediate level of protein structure description between protein domains and secondary structures. It is a new tool to better understand and analyze the organization of protein structures. PP2 uses only the matrices of protein contact probabilities and cuts the protein structures optimally using Matthews' coefficient correlation. An index assesses the compactness quality of each PU. Results are given both textually and graphically using JMol and PyMol softwares. The server can be accessed from http://www.ebgm.jussieu.fr/~gelly/index.html.

Computer Graphics↗
PubMed2005

A structural model of a seven-transmembrane helix receptor: the Duffy antigen/receptor for chemokine (DARC).

The Duffy antigen/receptor for chemokine (DARC) is an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi) and for chemokines. In contrast to other chemokine receptors, DARC is a promiscuous receptor that binds chemokines of both CC and CXC classes. The four extracellular domains (ECDs) of DARC are essential for its interaction with chemokines, whilst the first (ECD1) is sufficient for the interaction with malaria erythrocyte-binding protein. In this study, we elaborate and analyze structural models of the DARC. The construction of the 3D models is based on a comparative modeling process and on the use of many procedures to predict transmembrane segments and to detect far homologous proteins with known structures. Threading, ab initio, secondary structure and Protein Blocks approaches are used to build a very large number of models. The conformational exploration of the ECDs is performed with simulated annealing. The second and fourth ECDs are strongly constrained. On the contrary, the ECD1 is highly flexible, but seems composed of three consecutive regions: a small beta-sheet, a linker region and a structured loop. The chosen structural models encompass most of the biochemical features and reflect the known experimental data. They may be used to analyze functional interaction properties.

Amino Acid Sequence↗
PubMed2003

Dynamical properties of the MscL of Escherichia coli: a normal mode analysis.

The mechanosensitive channel (MscL) is an integral membrane protein which gates in response to membrane tension. Physiological data have shown that the gating transition involves a very large change in the conformation, and that the open state of the channel forms a large non-specific pore with a high conductance. The Escherichia coli channel structure was first modeled by homology modeling, starting with the X-ray structure of the homologous from Mycobacterium tuberculosis. Then, the dynamical and conformational properties of the channel were explored, using normal mode analysis. Such an analysis was also performed with the different structures proposed recently by Sukharev and co-workers. Similar dynamical behaviors are observed, which are characteristic of the channel architecture, subtle differences being due to the different relative positioning of the structural elements. The ability of particular regions of the channel to deform is discussed with respect to the functional and structural properties, implied in the gating process. Our results show that the first step of the gating mechanism can be described with three low-frequency modes only. The movement associated to these modes is clearly an iris-like movement involving both tilt and twist rotation.

Amino Acid Sequence↗
PubMed2000

Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks.

By using an unsupervised cluster analyzer, we have identified a local structural alphabet composed of 16 folding patterns of five consecutive C(alpha) ("protein blocks"). The dependence that exists between successive blocks is explicitly taken into account. A Bayesian approach based on the relation protein block-amino acid propensity is used for prediction and leads to a success rate close to 35%. Sharing sequence windows associated with certain blocks into "sequence families" improves the prediction accuracy by 6%. This prediction accuracy exceeds 75% when keeping the first four predicted protein blocks at each site of the protein. In addition, two different strategies are proposed: the first one defines the number of protein blocks in each site needed for respecting a user-fixed prediction accuracy, and alternatively, the second one defines the different protein sites to be predicted with a user-fixed number of blocks and a chosen accuracy. This last strategy applied to the ubiquitin conjugating enzyme (alpha/beta protein) shows that 91% of the sites may be predicted with a prediction accuracy larger than 77% considering only three blocks per site. The prediction strategies proposed improve our knowledge about sequence-structure dependence and should be very useful in ab initio protein modelling.

Artificial Intelligence↗
PubMed1999

Unraveling proteins: a molecular mechanics study.

An internal coordinate molecular mechanics study of unfolding peptide chains by external stretching has been carried out to predict the type of force spectra that may be expected from single-molecule manipulation experiments currently being prepared. Rather than modeling the stretching of a given protein, we have looked at the behavior of simple secondary structure elements (alpha-helix, beta-ribbon, and interacting alpha-helices) to estimate the magnitude of the forces involved in their unfolding or separation and the dependence of these forces on the way pulling is carried out as well as on the length of the structural elements. The results point to a hierarchy of forces covering a surprisingly large range and to important orientational effects in the response to external stress.

Biophysical Phenomena↗
PubMed1997

Prediction of protein side chain conformations: a study on the influence of backbone accuracy on conformation stability in the rotamer space.

We have studied the effect of backbone inaccuracy on the efficiency of protein side chain conformation prediction using rotamer libraries. The backbones were generated by randomly perturbing the crystallographic conformation of 12 proteins and exhibit C alpha r.m.s.d.s of up to 2 A. Our results show that, even for a perturbation of the backbone fully compatible with the temperature factors of the proteins, the predicted side chain conformations of approximately 10% of the buried side chains remain variable. This fraction increases further for larger backbone deviations. However, for backbone deviations of up to 2 A r.m.s.d., the predicted side chain r.m.s.d. varies only in a ratio of < 1.4. Moreover, a possible strategy for obtaining side chain conformations close to the experimental ones consists of extracting the consensus conformations of the side chains from a series of backbone conformations. Such a procedure allows the computation of the side chain conformations with no loss of accuracy for backbones exhibiting r.m.s.d.s of up to 1 A from the crystallographic coordinates. For larger backbone deviations (up to 2 A r.m.s.d.) the r.m.s.d. of the buried side chains increases from 1.33 up to 1.60 A. We also discuss the influence of the size of the rotamer library on the quality of the prediction.

Crystallography, X-Ray↗
PubMed1996

A model for the photosystem II reaction center core including the structure of the primary donor P680.

For a detailed understanding of the function of photosystem II (PSII), a molecular structure is needed. The crystal structure has not yet been determined, but the PSII reaction center proteins D1 and D2 show homology with the L and M subunits of the photosynthetic reaction center from purple bacteria. We have modeled important parts of the D1 and D2 proteins on the basis of the crystallographic structure of the reaction center from Rhodopseudomonas viridis. The model contains the central core of the PSII reaction center, including the protein regions for the transmembrane helices B, C, D, and E and loops B-C and C-D connecting the helices. In the model, four chlorophylls, two pheophytins, and the nonheme Fe2+ ion are included. We have applied techniques from computational chemistry that incorporate statistical data on side-chain rotameric states from known protein structure and that describe interactions within the model using an empirical potential energy function. The conformation of chlorophyll pigments in the model was optimized by using exciton interaction calculations in combination with potential energy calculations to find a solution that agrees with experimentally determined exciton interaction energies. The model is analyzed and compared with experimental results for the regions of P680, the redox active pheophytin, the acceptor side Fe2+, and the tyrosyl radicals TyrD and TyrZ. P680 is proposed to be a weakly coupled chlorophyll a pair which makes three hydrogen bonds with residues on the D1 and D2 proteins. In the model the redox-active pheophytin is hydrogen bonded to D1-Glu130 and possibly also to D1-Tyr126 and D1-Tyr147. TyrD is hydrogen bonded to D2-His190 and also interacts with D2-Gln165. TyrZ is bound in a hydrophilic environment which is partially constituted by D1-Gln165, D1-Asp170, D1-Glu189, and D1-His190. These polar residues are most likely involved in proton transfer from oxidized TyrZ or in metal binding.

Amino Acid Sequence↗
PubMed1994

Rotational orientation of transmembrane alpha-helices in bacteriorhodopsin. A neutron diffraction study.

The rotational orientation of the seven transmembrane alpha-helices (A-G) in bacteriorhodopsin has been investigated by neutron diffraction. The current model of bacteriorhodopsin is based on an electron density map obtained by high-resolution electron microscopy (EM). Assigning helix rotational positions in the EM model depended on fitting large side-chains, mainly aromatic residues, into bulges in the electron density map. For helix D, which contains no aromatic residues, the EM map is more difficult to interpret. For helices A and B, whose position and orientation had been determined previously by neutron diffraction, the positions defined by EM agree within experimental error with these earlier conclusions. The orientation of all seven helices has been examined by using neutron diffraction on bacteriorhodopsin samples with specifically deuterated valine, leucine and tryptophan residues. Experimental peak intensities were compared to those predicted for an extensive set of structural models. The models were generated by (1) rotating all helices around their axis; (2) moving deuterated residues in the extramembrane loops about their probable positions and changing the weight of their contribution to the neutron diffraction pattern; (3) allowing deuterated side-chains to change their conformation. The analysis confirmed exactly the positions previously determined for helices A and B. For an optimal fit to the data to be obtained, the other five helices, including helix D, must lie either at or within 20 degrees of their position in the current EM model. The complementarity of medium-resolution EM, neutron diffraction and model building for the structural study of integral membrane proteins is discussed.

Bacteriorhodopsins↗
PubMed1994

Prediction of the positioning of the seven transmembrane alpha-helices of bacteriorhodopsin. A molecular simulation study.

We have applied a search strategy for determining the optimal packing of protein secondary structure elements to the rotational positioning of the seven transmembrane helices of bacteriorhodopsin. The search is based on the assumption that the relative orientations of the helices within the bundle are conditioned principally by inter-helix side-chain interactions and that the extra-helical parts of the protein have only a minor influence on the bundle conformation. Our approach performs conformational energy optimization using a predetermined set of side-chain rotamers and appropriate methods for sampling the conformational space of peptide fragments with fixed backbone geometries. The final solution obtained for bacteriorhodopsin places each of the seven helices to a precision of a few degrees in rotation around the helical axis and to a few tenths of an ångström in translation along the helical axis with respect to the best experimental structure obtained by electron diffraction, except for helix D, where our results support the suggestion that this helix should be displaced along its axis toward its N terminus. The perspectives of such an approach for the determination of the structures of other transmembrane helical bundles are discussed.

Bacteriorhodopsins↗
PubMed1994

Hydrophobic neighboring homology (HNH) dotplot: an approach for assessing structurally similar motifs in proteins.

Structural biology needs sensitive tools to detect homology between proteins of low sequence identity, but with closely related 3-D structures. Using a conventional dotplot method, we therefore introduced 2 concepts to improve the search for similarities between secondary structures of analyzed proteins: 'hydrophobic neighboring homology' (HNH) and 'amino acid degeneracy classes'. The amino acids are grouped into 3 subsets: hydrophobic, hydrophilic and mimetic. A 'Neighboring Similarity Index' (NSI) is calculated for every residue pair and quantifies its neighbor homology. By thresholding the homology matrix and filtering the dotplot, the homologous patterns are extracted. We have evaluated the efficiency and limits of the method using 21 protein pairs extracted from the Protein Data Bank (PDB), or selected from the recent literature. Globally, we again find the homologous structures (alpha-helices and beta-strands) of these pair proteins. The introduction of neighbor residue hydrophobicity in the conventional dotplot improves the alignment of proteins with low sequence identity (< 25%). HNH, written in standard ANSI C with the graphic library X11, under UNIX, is available on request.

Cluster Analysis↗
PubMed1993

Structure and dynamics of bacteriorhodopsin. Comparison of simulation and experiment.

Global features of the structure and dynamics of bacteriorhodopsin are investigated using molecular modelling, dynamical simulations and neutron scattering experiments. The simulations are performed on a model system consisting of one protein molecule plus intrinsic water molecules. The simulation-derived structure is compared with neutron diffraction data on the location of water and with the available electron microscopy structure of highest resolution. The simulated water geometry is in good accord with the neutron data. The protein structure deviates slightly but significantly from the experiment. The low-frequency vibrational frequency distribution of a low-hydration purple membrane is derived from inelastic neutron scattering data and compared with the corresponding simulation-derived quantity.

Bacteriorhodopsins↗
PubMed1993

Comparison of three algorithms for the assignment of secondary structure in proteins: the advantages of a consensus assignment.

Accurate assignments of secondary structures in proteins are crucial for a useful comparison with theoretical predictions. Three major programs which automatically determine the location of helices and strands are used for this purpose, namely DSSP, P-Curve and Define. Their results have been compared for a non-redundant database of 154 proteins. On a residue per residue basis, the percentage match score is only 63% between the three methods. While these methods agree on the overall number of residues in each of the three states (helix, strand or coil), they differ on the number of helices or strands, thus implying a wide discrepancy in the length of assigned structural elements. Moreover, the length distribution of helices and strands points to the existence of artefacts inherent to each assignment algorithm. To overcome these difficulties a consensus assignment is proposed where each residue is assigned to the state determined by at least two of the three methods. With this assignment the artefacts of each algorithm are attenuated. The residues assigned in the same state by the three methods are better predicted than the others. This assignment will thus be useful for analysing the success rate of prediction methods more accurately.

Algorithms↗
PubMed1991

A new approach to the rapid determination of protein side chain conformations.

Two efficient algorithms have been developed which allow amino acid side chain conformations to be optimized rapidly for a given peptide backbone conformation. Both these approaches are based on the assumption that each side chain can be represented by a small number of rotameric states. These states have been obtained by a dynamic cluster analysis of a large data base of known crystallographic structures. Successful applications of these algorithms to the prediction of known protein conformations are presented.

Algorithms↗
PubMed1990

Conformational and helicoidal analysis of the molecular dynamics of proteins: "curves," dials and windows for a 50 psec dynamic trajectory of BPTI.

A new procedure for the graphic analysis of molecular dynamics (MD) simulations on proteins is introduced, in which comprehensive visualization of results and pattern recognition is greatly facilitated. The method involves determining the conformational and helicoidal parameters for each structure entering the analysis via the method "Curves," developed for proteins by Sklenar, Etchebest, and Lavery (Proteins: Structure, Function Genet. 6:46-60, 1989) followed by a novel computer graphic display of the results. The graphic display is organized systematically using conformation wheels ("dials") for each torsional parameter and "windows" on the range values assumed by the linear and angular helicoidal parameters, and is present in a form isomorphous with the primary structure per se. The complete time evolution of dynamic structure can then be depicted in a set of four composite figures. Dynamic aspects of secondary and tertiary structure are also provided. The procedure is illustrated with an analysis of a 50 psec in vacuo simulation on the 58 residue protein, bovine pancreatic trypsin inhibitor (BPTI), in the vicinity of the local minimum on the energy surface corresponding to a high resolution crystal structure. The time evolution of 272 conformational and 788 helicoidal parameters for BPTI is analyzed. A number of interesting features can be discerned in the analysis, including the dynamic range of conformational and helicoidal motions, the dynamic extent of 2 degrees structure motifs, and the calculated fluctuations in the helix axis. This approach is expected to be useful for a critical analysis of the effects of various assumptions about force field parameters, truncation of potentials, solvation, and electrostatic effects, and can thus contribute to the development of more reliable simulation protocols for proteins. Extensions of the analysis to present differential changes in conformational and helicoidal parameters is expected to be valuable in MD studies of protein complexes with substrates, inhibitors, and effectors and in determining the nature of structural changes in protein-protein interactions.

Biological Evolution↗
PubMed1989

Describing protein structure: a general algorithm yielding complete helicoidal parameters and a unique overall axis.

We present a general and mathematically rigorous algorithm which allows the helicoidal structure of a protein to be calculated starting from the atomic coordinates of its peptide backbone. This algorithm yields a unique curved axis which quantifies the folding of the backbone and a full set of helicoidal parameters describing the location of each peptide unit. The parameters obtained form a complete and independent set and can therefore be used for analyzing, comparing, or reconstructing protein backbone geometry. This algorithm has been implemented in a computer program named P-Curve. Several examples of its possible applications are discussed.

Algorithms↗
PubMed1988

Energy profile of Cs+ in gramicidin A in the presence of water. Problem of the ion selectivity of the channel.

The effect of water present at the mouth and inside the channel of Gramicidin A on the energy profile calculated for a caesium ion is determined. The total optimal interaction energy computed for the system GA-Cs+-(22 waters) leads to an energy profile characterized by a deep minimum at 11 A followed by an entrance energy barrier of 7 Kcal/mol expanding until 9 A from the center. After this point, a second minimum less deep than the previous one is observed, itself followed by a central barrier. The shape of the profile at the entrance is governed by the balance between the progressive desolvation process of the ion and the increase of favorable hydrogen bond interactions implying both the water molecules and GA. The comparison of this energy profile with that obtained in vacuo shows that the presence of water molecules does not modify the pathway of the ion which, owing to its size, is constrained essentially to remain on the channel axis. The comparison Na+ versus Cs+ indicates that although the phenomena involved are globally the same, differences between the two profiles appear due firstly to the difference in the affinity of the two ions for water and secondly to their respective size. This last difference implies that the number of water molecules present in the interior of the channel during the cation progression is reduced roughly by one in the case of caesium. The desolvation barrier computed for Cs+ is half the corresponding value for Na+, a result in agreement with the observed selectivity.

Biological Transport↗
PubMed1986

The gramicidin A channel: energetics and structural characteristics of the progression of a sodium ion in the presence of water.

The distribution of water molecules in the Gramicidin A (GA) channel is determined by theoretical computations, and the role of this water on the energetics of the system upon progression of a sodium cation through the channel is investigated. In the absence of the ion, water molecules form a chain along the channel, hydrogen bonded to one another and to the L carbonyl oxygens, while others stay at the entrances of the channel, hydrogen-bonded to the free carbonyl oxygens of the L-Tryptophan residues. According to the definition adopted for the "inside" and the "outside" of the channel, it is found to contain at most 7 or 9 water molecules. When a hydrated sodium cation approaches and enters the channel, the structural properties corresponding to the minimized total energy of the system GA-water-Na+ indicate a reorganization, but not a destruction, of the chain of water molecules. The "energy profile" for the system GA-Na+-(22 waters) is analyzed in terms of its components and in comparison to the corresponding intrinsic profile computed earlier in vacuo. It appears that the presence of water does not unduely modify the pathway or the qualitative features of the energetics of the cation passage, except at the entrance, where the partial and progressive dehydration of the cation plays an important role. The presence and characteristics of the minimum found earlier at 10.5 A from the center are conserved.

Gramicidin↗