共查询到20条相似文献,搜索用时 93 毫秒
1.
We address the problem of the prediction of residue spatial proximity in a protein, through the automatic processing of a
3D 15N NOESY–HSQC. The spatial distance between residues is estimated from a spectral match value calculated using a comparison
of the resonances involving the amide hydrogens. The method is shown to provide a good estimation of a large number of residue
spatial proximities, in the case of two experimental 3D spectra, recorded on proteins of α and β secondary structures. It
is tested on simulated data sets against the protein size, secondary structure and the quality of the signal. More than 70%
of the sequential assignment is correctly predicted, and the prediction is better for the α than for the β secondary structure.
The medium- and long-range correlations seem equally well predicted for all the secondary structures. The efficiency of the
method is compared to a previously proposed spectral correlation approach.
Received: 5 July 2000 / Accepted: 8 September 2000 / Published online: 19 January 2001 相似文献
2.
Interactions among residues together with their interactions with the surrounding medium determine the unique structure of
globular proteins. An algorithm was recently developed to locate residues participating in cooperative long-range interactions,
called stabilization center residues, that are primarily responsible for preventing the decay of the 3D structure. While our
statistical analysis showed that interactions of stabilization center residues hardly influence the formation of the various
secondary structure elements, the distribution of the stabilization center residues is rather uneven among the secondary structure
elements. Here we analyzed the frequency and distribution of the stabilization center residues and their interacting pairs
in secondary structure classes to learn about the effect of secondary structure on the formation and properties of stabilization
centers and about the types of interactions responsible for stabilization of proteins of various secondary structure classes.
It was found that residues from the same secondary structure tend to interact with each other in the stabilization centers
of all classes. It is also suggested that the folding-unfolding equilibrium is governed by different principles for class
all-α than for the rest of the classes.
Received: 24 April 1998 / Accepted: 17 September 1998 / Published online: 7 December 1998 相似文献
3.
The positions of a given fold always occupied by strong hydrophobic amino acids (V, I, L, F, M, Y, W), which we call “topohydrophobic
positions”, were detected and their properties demonstrated within 153 non-redundant families of homologous domains, through
3D structural alignments. Sets of divergent sequences possessing at least four to five members appear to be as informative
as larger sets, provided that their mean pairwise sequence identity is low. Amino acids in topohydrophobic positions exhibit
several interesting features: they are much more buried than their equivalents in non-topohydrophobic positions, their side
chains are far less dispersed; and they often constitute a lattice of close contacts in the inner core of globular domains.
In most cases, each regular secondary structure possesses one to three topohydrophobic positions, which cluster in the domain
core. Moreover, using sensitive alignment processes such as hydrophobic cluster analysis (HCA), it is possible to identify
topohydrophobic positions from only a small set of divergent sequences. Amino acids in topohydrophobic positions, which can
be identified directly from sequences, constitute key markers of protein folds, define long-range structural constraints,
which, together with secondary structure predictions, limit the number of possible conformations for a given fold.
Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 16 November 1998 相似文献
4.
M. Compiani P. Fariselli P. L. Martelli R. Casadio 《Theoretical chemistry accounts》1999,101(1-3):21-26
Protein secondary structures result both from short-range and long-range interactions. Here neural networks are used to implement
a procedure to detect regions of the protein backbone where local interactions have an overwhelming effect in determining
the formation of stretches in α-helical conformation. Within the framework of a modular view of protein folding we have argued
that these structures correspond to the initiation sites of folding. The hypothesis to be tested in this paper is that sequence
identity beside ensuring similarity of the three-dimensional conformation also entails similar folding mechanisms. In particular,
we compare the location and sequence variability of the initiation sites extracted from a set of proteins homologous to horse
heart cytochrome c. We present evidence that the initiation sites conserve their position in the aligned sequences and exhibit a more reduced
variability in the residue composition than the rest of the protein.
Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 11 November 1998 相似文献
5.
Krzysztof A. Olszewski Lisa Yan David J. Edwards 《Theoretical chemistry accounts》1999,101(1-3):57-61
SeqFold is a fold recognition program based on sequence-similarity detection aided by predicted secondary structure [1–3].
Critical validation and evaluation of SeqFold fold recognition performance based on the latest Critical Assessment of protein
Structure Prediction (CASP2) targets has been performed. It has revealed that four out of seven CASP2 threading targets were
assigned a correct fold using this method. SeqFold has also been applied to the problem of fold recognition for leptin. Mice
with a defective leptin gene are extremely obese and diabetic. Leptin does not exhibit clear sequence homology to any protein
with known structure. SeqFold predicts that leptin belongs to the class of short-chain four-helical cytokines. The structure
of leptin, which has recently been solved by X-ray crystallography, reveals that leptin is a long-chain four-helical cytokine.
The 3D model of leptin demonstrates that SeqFold alignment-based homology modeling captures essential features of the leptin
structure.
Received: 25 May 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998 相似文献
6.
A statistical analytical approach has been used to analyze the secondary structure (SS) of amino acids as a function of the
sequence of amino acid residues. We have used 306 non-homologous best-resolved protein structures from the Protein Data Bank
for the analysis. A sequence region of 32 amino acids on either side of the residue is considered in order to calculate single
amino acid propensities, di-amino acid potentials and tri-amino acid potentials. A weighted sum of predictions obtained using
these properties is used to suggest a final prediction method. Our method is as good as the best-known SS prediction methods,
is the simplest of all the methods, and uses no homologous sequence/family alignment data, yet gives 72% SS prediction accuracy.
Since the method did not use many other factors that may increase the prediction accuracy there is scope to achieve greater
accuracy using this approach.
Received: 4 May 1998 / Accepted: 17 September 1998 / Published online: 10 December 1998 相似文献
7.
A discrete-state ab initio protein structure prediction procedure is presented, based on the assumption that some proteins
fold in an hierarchical way, where the early folding of independent units precedes and helps complete structure formation.
It involves a first step predicting, by means of threading algorithms and local structure prediction methods, the location
of autonomous protein subunits presenting favorable local and tertiary interactions. The second step consists of predicting
the structure of these units by Monte Carlo simulated annealing using several database-derived potentials. In a last step,
these predicted structures are used as starting conformations of additional simulations, keeping these structures frozen and
including the complete protein sequence. This procedure is applied to two small DNA-binding proteins, 434 cro and the Drosophila melanogaster homeodomain that contain 65 and 47 residues, respectively, and is compared to the nonhierarchical procedure where the whole
protein is predicted in a single run. The best predicted structures were found to present root-mean-square deviations relative
to the native conformation of 2.7 ? in the case of the homeodomain and of 3.9 ? for 434 cro; these structures thus represent
low-resolution models of the native structures. Strikingly, not only the helices were correctly predicted but also intervening
turn motifs.
Received: 6 July 2000 / Accepted: 8 September 2000 / Published online: 21 December 2000 相似文献
8.
Jean-Pierre Duneau Serge Crouzy Yves Chapron Monique Genest 《Theoretical chemistry accounts》1999,101(1-3):87-91
The structure and dynamics of the ErbB-2 transmembrane domain have been examined using molecular dynamics techniques both
in vacuum and within an explicit hydrated L-α-dilauroyl-phosphatidyl-ethanolamine environment. In-vacuum simulations show that a highly cooperative structural transition
occurs frequently within the α-helical transmembrane domain which converts to local π-helices. We show that the α-helix alteration
does not depend upon the force field or initial side-chain conformations but is intimately related to the sequence. The membrane-like
environment does not prevent the structural transition in the helix but slows down the peptide dynamics indicating that the
appearance of a π-bulge is not an artifact of the vacuum approximation. The consequences of π-helix formation could be very
huge for the ErbB-2 receptor which is involved in numerous human cancers and also for other membrane proteins wherein similar
local structures are also observed experimentally.
Received: 9 May 1998 / Accepted: 3 September 1998 / Published online: 17 December 1998 相似文献
9.
The diversity of RNA tertiary structures provides the basis for specific recognition by proteins or small molecules. To investigate
the structural basis and the energetics which control RNA-ligand interactions, favorable RNA binding sites are identified
using the MCSS method, which has been employed previously only for protein receptors. Two different RNAs for which the structures
have been determined by NMR spectroscopy were examined: two structures of the TAR RNA which contains an arginine binding site,
and the structure of the 16S rRNA which contains an aminoglycoside binding site (paromomycin). In accord with the MCSS methodology,
the functional groups representing the entire ligand or only part of it (one residue in the case of the aminoglycosides) are
first replicated and distributed with random positions and orientations around the target and then energy minimized in the
force field of the target RNA. The Coulombic term and the dielectric constant of the force field are adjusted to approximate
the effects of solvent-screening and counterions. Optimal force field parameters are determined to reproduce the binding mode
of arginine to the TAR RNA. The more favorable binding sites for each residue of the aminoglycoside ligands are then calculated
and compared with the binding sites observed experimentally. The predictability of the method is evaluated and refinements
are proposed to improve its accuracy.
Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 7 December 1998 相似文献
10.
V. Moliner J. Andrés M. Oliva V. S. Safont O. Tapia 《Theoretical chemistry accounts》1999,101(1-3):228-233
The present study elucidates structural features related to the molecular mechanism in the carboxylation step of the reaction
catalyzed by Rubisco. Starting from the initial X-ray Protein Data Bank structure of a Rubisco monomer, the reactive subsystem
in vacuo is subjected to quantum chemical semiempirical and ab initio studies, while the effects of the protein environments
are included by means of a hybrid quantum mechanical/molecular mechanical (QM/MM) approach. The QM/MM is used to characterize
the transition structure for carboxylation inside the protein. The calculations were made with the AM1/CHARMM/GRACE scheme.
Comparisons between the in vacuo and in situ transition structures show remarkable invariance with respect to geometric parameters,
index and transition vector amplitudes. The transition state couples the carbon dioxide attack to the C2 center of the substrate
in its dienol form with a simultaneous intramolecular hydrogen transfer from the C2 atom to the hydroxyl group linked to the
C3 center. This study suggests that carboxylation may be simultaneously coupled to the activation of the C3 center in the
enzyme.
Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 10 December 1998 相似文献
11.
J.-M. Moulis 《Theoretical chemistry accounts》1999,101(1-3):223-227
Rubredoxins are small electron transfer proteins containing one iron atom at their active site. The rubredoxin from the anaerobic
bacterium Clostridium pasteurianum has been subjected to molecular dynamics studies starting from the minimized solvated structure. The results of the simulations
have been compared with identical ones carried out with selected mutated forms of the protein obtained by molecular modeling.
Surface residues, which are highly conserved among rubredoxins and close to the cysteine ligands, can be replaced by glutamates,
i.e. long chain carboxylates. The main structural consequence is a shift of the protein backbone bearing conserved aromatic
residues. Reciprocally, substitution of the aromatic residue closest to the iron atom shifts the cysteine-containing peptide
fragments. These observations have been related to the changes in electron transfer and redox properties previously measured
for this set of rubredoxin molecular variants.
Received: 16 May 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998 相似文献
12.
Coupled advances in empirical force fields and classical molecular dynamics simulation methodologies, combined with the availability
of faster computers, has lead to significant progress towards accurately representing the structure and dynamics of biomolecular
systems, such as proteins, nucleic acids, and lipids in their native environments. Thanks to these advances, simulation results
are moving beyond merely evaluating force fields, displaying expected structural fluctuations, or demonstrating low root-mean-squared
deviations from experimental structures and now provide believable structural insight into a variety of processes such as
the stabilization of A-DNA in mixed water and ethanol solution or reversible β-peptide folding in methanol. The purpose of this overview is to take stock of these recent advances in biomolecular simulation
and point out some common deficiencies exposed in longer simulations. The most significant methodological advances relate
to the development of fast methods to properly treat long-range electrostatic interactions, and in this regard the fast Ewald
methods are becoming the de facto standard.
Received: 9 April 1998 / Accepted: 21 May 1998 / Published online: 13 August 1998 相似文献
13.
The “hybrid protein model” is a fuzzy model for compacting local protein structures. It learns a nonredundant database encoded
in a previously defined structural alphabet composed of 16 protein blocks (PBs). The hybrid protein is composed of a series
of distributions of the probability of observing the PBs. The training is an iterative unsupervised process that for every
fold to be learnt consists of looking for the most similar pattern present in the hybrid protein and modifying it slightly.
Finally each position of the hybrid protein corresponds to a set of similar local structures. Superimposing those local structures
yields an average root mean square of 3.14 ?. The significant amino acid characteristics related to the local structures are
determined. The use of this model is illustrated by finding the most similar folds between two cytochromes P450.
Received: 13 June 2000 / Accepted: 18 September 2000 / Published online: 19 January 2001 相似文献
14.
The remarkable conservation of protein structure, compared to that of sequences, suggests that, in the course of evolution,
residue substitutions which tend to destabilise a particular structure must be compensated by other substitutions that confer
greater stability on that structure. Given the compactness of proteins, spatially close residues are expected to undergo the
compensatory process. Surprisingly, approaches designed to detect such correlated changes have led, until now, only to limited
success in detecting pairs of residues adjacent in the three-dimensional structures. We have undertaken, by simulating the
evolution of DNA sequences including sites mutating in a correlated manner, to analyse whether such poor results can be attributed
to the detection methods or if this failure could result from a compensatory process more complex than that implicitly underlying
the different approaches. Present results show that only methods taking into account the phylogenetic reconstruction can lead
to correct detection.
Received: 24 April 1998 / Accepted: 8 August 1998 / Published online: 11 November 1998 相似文献
15.
Tru Huynh Gabriel Musat Jean-Michel Neumann Jeremy C. Smith Alain Sanson 《Theoretical chemistry accounts》1999,101(1-3):82-86
Annexin molecules consist of a symmetrical arrangement of four domains of identical folds but very different sequences. Nuclear
magnetic resonance (NMR) experiments on the isolated domains of annexin I in aqueous solution have indicated that domain 1
retains its native structure whereas domain 2 unfolds. Therefore these two domains constitute interesting models for comparative
simulations of structural stability using molecular dynamics. Here we present the preliminary results of molecular dynamics
simulations of the isolated domain 1 in explicit water at 300 K, using two different simulation protocols. For the first,
domain 1 was embedded in a 46 ? cubic box of water. A group-based non-bonded cut-off of 9 ? with a 5–9 ? non-bonded switching
function was used and a 2 fs integration step. Bonds containing hydrogens were constrained with the SHAKE algorithm. These
conditions led to unfolding of the domain within 400 ps at 300 K. In the second protocol, the domain was embedded in a 62 ?
cubic box of water. An atom-based non-bonded cut-off of 8–12 ? using a force switching function for electrostatics and a shifting
function for van der Waals interactions were used with a 1 fs integration step. This second protocol led to a native-like
conformation of the domain in accord with the NMR data which was stable over the whole trajectory (∼2 ns). A small, but well-defined
relaxation of the structure, from that observed for the same domain in the entire protein, was observed. This structural relaxation
is described and methodological aspects are discussed.
Received: 10 May 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998 相似文献
16.
Molecular mechanics calculations were performed with the JUMNA program on d(GCGTGOGTGCG) · d(CGCACTCACGC) where “O” is a
modified abasic site: 3-hydroxy-2-(hydroxymethyl)tetrahydrofuran. From energy minimizations, for intrahelical or extrahelical
positions of the unpaired thymine, various structures with different curvatures were obtained. Dynamical properties of this
abasic sequence were also investigated through the controlled studies of DNA bending. Poisson-Boltzmann calculations were
used to mimic the electrostatic effect of solvent on this sequence. The lowest energy structures show an acceptable agreement
with experimental data.
Received: 1 June 1998 / Accepted: 17 September 1998 / Published online: 10 December 1998 相似文献
17.
Aishui Yu Naoaki Kumagai Zhaolin Liu Jim Y. Lee 《Journal of Solid State Electrochemistry》1998,2(6):394-400
Hexagonal and monoclinic tungsten trioxides WO3 and hexagonal lithium tungstates Li
x
WO3+
x
/2 (x = 0.10–0.42) from a soft chemistry route were used as the active cathode material in secondary lithium batteries. The hexagonal
structures, regardless of their being an oxide or a tungstate, showed higher specific capacities and better cycling behavior
in Li+ intercalation reactions than the monoclinic form. The presence of pre-allocated lithium (as Li2O) in hexagonal tungstates decreased the capacity for lithium intercalation. Additionally, the plot of open-circuit voltage
(OCV) against the depth of intercalation (n) for anhydrous tungstates showed two straight lines with different slopes that can be related to the structural changes in
lithium intercalation. The effective diffusion coefficients of lithium insertion into the host structure, D˜, were also found to be dependent on the structure and the composition of these compounds.
Received: 28 November 1997 / Accepted: 6 March 1998 相似文献
18.
The use of Brownian dynamics simulations to investigate the presence of structural (kinks) and dynamic (bulges) anomalies
in short DNA stretches is analyzed in connection with a string-of-beads model. A scaling method to choose the hydrodynamic
translational and rotational parameters of the beads is proposed and tested on straight, kinked and bulged DNA fragments 17 nm
long. The model reproduces the rigid-body rotational diffusion for the straight DNA and for the fluorescence polarization
anisotropy decay of the kinked and bulged DNAs the model predicts a different behavior which is found experimentally.
Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 23 November 1998 相似文献
19.
20.
Substituent effects on the structure of radicals and parent hydrocarbons formed by isolated or condensed three-membered rings
have been investigated by Hartree-Fock, post-Hartree-Fock and density functional methods. The trends of structural parameters
computed for the hydrocarbon systems are in agreement with available experimental data. Substituent effects can be rationalized
in terms of interactions between localized orbitals obtained by natural bond analysis. The effects are even larger in free
radicals and can be analyzed using the same model.
Received: 13 March 1998 / Accepted: 13 July 1998 / Published online: 9 October 1998 相似文献