共查询到20条相似文献,搜索用时 41 毫秒
1.
Á. Simon Z. Dosztányi C. Magyar G. Szirtes É. Rajnavölgyi I. Simon 《Theoretical chemistry accounts》2001,106(1-2):121-127
The well-balanced stability of protein structures allows large-scale fluctuations, which are indispensable in many biochemical
functions, ensures the long-term persistence of the equilibrium structure and it regulates the degradation of proteins to
provide amino acids for biosynthesis. This balance is studied in the present work with two sets of proteins by analyzing stabilization
centers, defined as certain clusters of residues involved in cooperative long-range interactions. One data set contains 56
proteins, which belong to 16 families of homologous proteins, derived from organisms of various physiological temperatures.
The other set is composed of 31 major histocompatibility complex (MHC)–peptide complexes, which represent peptide transporters
complexed with peptide ligands that apparently contribute to the stabilization of the MHC proteins themselves. We show here
that stabilization centers, which had been identified as special clusters of residues that protect the protein structure,
evolved to serve also as regulators of function – related degradation of useless protein as part of protein housekeeping.
Received: 25 August 2000 / Accepted: 6 September 2000 / Published online: 21 December 2000 相似文献
2.
One of the purposes of studying protein stability changes upon mutations is to get information about the dominating interactions
that drive folding and stabilise the native structure. With this in mind, we present a method that predicts folding free-energy
variations caused by point mutations using combinations of two types of database-derived potentials, i.e. backbone torsion-angle
potentials and distance potentials, describing local and non-local interactions along the chain, respectively. The method
is applied to evaluate the folding free-energy changes of 344 single-site mutations introduced in six different proteins and
a synthetic peptide. We found that the relative importance of local versus non-local interactions along the chain is essentially
a function of the solvent accessibility of the mutated residues. For the subset of totally buried residues, the optimal potential
is the sum of a distance potential and a torsion potential weighted by a factor of 0.4. This combination yields a correlation
coefficient between measured and computed changes in folding free energy of 0.80. For mutations of partially buried residues,
the best potential is the sum of a torsion potential and a distance potential weighted by 0.7. For fully accessible residues,
the torsion potentials taken alone perform best, reaching correlation coefficients of 0.87 on all but 10 mutations; the excluded
mutations seem to modify the backbone structure or to involve interactions that are atypical for the surface. These results
show that the relative weight of non-local interactions along the sequence decreases as the solvent accessibility of the mutated
residue increases, and vanishes at the protein surface. On the contrary, the weight of local interactions increases with solvent
accessibility. The latter interactions are nevertheless never negligible, even for the most buried residues.
Received: 20 May 1998 / Accepted: 3 September 1998 / Published online: 7 December 1998 相似文献
3.
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
4.
A. C. Camproux P. Tuffery L. Buffat C. André J. F. Boisvieux S. Hazout 《Theoretical chemistry accounts》1999,101(1-3):33-40
Hidden Markov models were used to identify recurrent short 3D structural building blocks (SSBBs) describing protein backbones.
Polypeptide chains were broken down into successive short segments defined by their inter-alpha-carbon distances. Fitting
the model to a database of nonredundant proteins identified 12 distinct SSBBs and described the preferred pathways by which
SSBBs were assembled to form the 3D structure of the proteins. Protein backbones were labelled in terms of these SSBBs. The
observed SSBB preferences for fragments located between regular secondary structures suggested that they depended more on
the following regular structure than on the preceding one. Extraction of repeated series of SSBBs between regular secondary
structures showed some structural specificity within different connection types. These results confirm that SSBBs can be used
as building blocks for analyzing protein structures, and can yield new information on the structures of the coils flanking
secondary structures.
Received: 14 May 1998 / Accepted: 4 August 1998 / Published online: 16 November 1998 相似文献
5.
Sanna Jääskeläinen Chandra S. Verma Roderick E. Hubbard Leo S. D. Caves 《Theoretical chemistry accounts》1999,101(1-3):175-179
The conformational change associated with the interfacial activation of Rhizomucor miehei lipase involves the displacement of an α-helical lid (residues 82–96) away from the active site on moving from water (high
dielectric) to lipid (low dielectric). The presence of two media of very different dielectric properties suggests that electrostatic
interactions play an important role in this process. We have used linearized Poisson–Boltzmann calculations to examine the
key electrostatic interactions which contribute to lid stability in the closed and open states. It is the two charged residues
of the lid, Arg86 and Asp91, that form the strongest electrostatic interactions with the rest of the protein. We identify
key residues whose interactions with the lid are significantly perturbed by the change in the dielectric of the medium: Asp61,
Arg80, Lys109, Glu117 and the active-site residues Asp203 and Asp256, all of which lie within approximately 20 ? of the lid.
We suggest that these residues are good candidates for site-specific mutation studies, which could help elucidate their role
in the lipase activation mechanism.
Received: 27 May 1998 / Accepted: 17 September 1998 / Published online: 7 December 1998 相似文献
6.
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
7.
Careful comparison of proteins sharing a same fold but only low or no sequence identity should allow a better understanding
of the coding of three-dimensional structures by amino acid sequences. It has already been shown that positions of a given
fold occupied mainly by hydrophobic residues in the different proteins of a structural family share very specific physical
properties and participate in stabilization of the protein domain. They probably also play a crucial role in the very first
steps of folding [ Poupon A, Mornon J.-P (1999) FEBS Lett. 452: 283–289; Mirny LA, Shaknovich EI (1999) J. Mol. Biol. 291: 177–196]. To further understand the sequence–structure relationship, we studied the correlation between allowed mutations
at a given three-dimensional position and some of its physical properties. The different amino acids were divided in three
groups (hydrophobic, nonpolar or weakly polar and polar or charged), and a correlation was established between the occupation
rate of each group at a given position in the fold and the burying, the side-chain dispersion, the interposition distances
and the ability to form a network of directly interacting residues. The results are then applied to predict some solvent accessibility.
We show that this property can be accurately predicted for about 70% of the residues, providing precious information concerning
the corresponding three-dimensional structures. The results are used to predict other structural features, as secondary structures,
compactness or long-range interactions between residues remote in sequence. This information will allow the number of possible
structures for a given sequence to be reduced considerably, simplifying the ab initio modelling problem to a level where it
might be solved by computing methods.
Received: 7 October 2000 / Accepted: 5 January 2001 / Published online: 3 April 2001 相似文献
8.
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
9.
Sudha Anand Anand Anbarasu Rao Sethumadhavan 《Applied biochemistry and biotechnology》2009,159(2):343-354
Glycoproteins are an important class of proteins that play a significant role in many cellular events. In the present study,
we analyze the influence of C–H…O interactions in relation to other environmental preferences in glycoproteins. CH…O interactions
are now accepted as a genuine hydrogen bond. Main chain–main chain interactions are predominant. Proline residues stabilize
strands by C–H…O interactions in glycoproteins. Majority of the C–H…O interacting residues were conserved and had one or more
stabilization centers. CH…O interactions might be responsible for the global conformational stability, since long-range CH…O
contacts were predominant. The results presented in this study might be useful for structural stability studies in glycoproteins. 相似文献
10.
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
11.
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
12.
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
13.
Jianwei Che Tahir Çağın William A. Goddard III 《Theoretical chemistry accounts》1999,102(1-6):346-354
We present a general approach for describing chemical processes (bond breaking and bond formation) in materials using force
fields (FF) that properly describe multiple bonds at small distances while describing nonbond (Coulomb and van der Waals)
interactions at long distances. This approach is referred to as the generalized extended empirical bond-order dependent FF.
In this paper we use the Brenner empirical bond-order dependent FF for the short-range interactions and report applications
on the energetics and structures of graphite crystal, dynamics of molecular crystals, and distortions of bucky tubes.
Received: 7 August 1998 / Accepted: 26 October 1998 / Published online: 16 March 1999 相似文献
14.
Alain Cartier David Brown Bernard Maigret Sandrine Boschi-Muller Sophie Rahuel-Clermont Guy Branlant 《Theoretical chemistry accounts》1999,101(1-3):241-245
In the framework of a theoretical approach to the relationship between structure and reactivity of the catalytic centers
of enzymes, glyceraldehyde-3 phosphate dehydrogenase (GAPDH) has been chosen as a model enzyme. In GAPDH, the proximity of
His176 increases the reactivity of Cys149 at neutral pH; however, its presence alone is not sufficient to explain the reactivity of the catalytic Cys. In order to
determine which other interactions play an important role, a study of the geometric and electronic structure of the catalytic
site has been made using a hybrid quantum mechanics/molecular mechanics local self-consistent field method. This allows the
computation of the electronic properties of amino acid residues in subsystems influenced by other parts of the macromolecule.
The quantum subsystem was centered on the Cys149 residue of GAPDH. The structures of GAPDH taken from the crystallographic database did not include hydrogen atoms and these
had to be added taking into account the fact that, in the active site, His176 has three tautomeric forms: δ-His protonated, ε-His protonated and His+. The results presented here suggest that the most stable His…Cys system in GAPDH is a strongly hydrogen-bonded Cys149
−/His176
+ ion pair.
Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 23 November 1998 相似文献
15.
Christopher J. Parkinson Paul M. Mayer Leo Radom 《Theoretical chemistry accounts》1999,102(1-6):92-96
Stabilization energies for the 1-cyanovinyl radical (CH2=CCN) have been calculated using a variety of conventional ab initio (M?ller–Plesset, quadratic configuration interaction
and coupled-cluster) and density functional theory (B-LYP, B3-LYP) procedures, as well as with a range of compound methods.
Compared with a high-level benchmark value (that predicts a stabilization energy of 17.1 kJ mol−1), UMP2 and UMP4 give the wrong sign and magnitude of the stabilization energy (both methods predicting desta- bilization
instead of stabilization), while B-LYP and B3-LYP overestimate the degree of stabilization. The RMP2, RMP4, QCISD(T) and CCSD(T)
techniques, and several, but not all, variants of G2 and CBS theories give radical stabilization energies in good agreement
with the benchmark value.
Received: 15 June 1998 / Accepted: 19 August 1998 / Published online: 15 February 1999 相似文献
16.
A combinatorial approach to fully conjugated acyclic polyenes (C
N
H
N
+2) is considered with a view to the extension of standard enumeration techniques to treat a widened range of chemically interesting
features. As a first step, enumerations are made respecting: placement of single and double bonds, the occurrence of cis/trans isomers, and the degree (and type) of “radicality” of such conjugated networks. As a further extension, several structural
(graph-theoretic) invariants averaged over various types of isomer classes and sub-classes are made, and then these invariants
are utilized to estimate several physicochemical properties averaged over these same classes or sub-classes. The properties
currently so considered are heats of formation, indices of refraction, and magnetic susceptibilities. Finally, the asymptotic
behaviors of isomer counts and isomer properties in the many-atom limit is elaborated.
Received: 10 August 1998 / Accepted: 17 November 1998 / Published online: 16 March 1999 相似文献
17.
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
18.
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
19.
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
20.
Molecular modelling calculations based on experimental data obtained in solution and in small unilamellar vesicles are used
to study interactions between amphiphilic basic peptides and membranes. The behaviour of such peptides during the initial
and final stages of the adsorption process is our primary interest. Primary sequences of 20 amino acid residues were designed
with equal numbers of basic lysines and hydrophobic leucines in order to get an amphipathic α helix. First, in solution, aggregates
with an increasing number (up to nine) of helical monomers were built up and the hydrophobic solvent accessible surface per
monomer was analysed on energy minimised structures. This showed that aggregates with 5–8 of monomers should be equally probable,
in reasonable accordance with experimental data. In addition, models of membranes with 21 dimyristoyl-phosphatidylcholine
lipids were constructed; amphiphilic peptides were merged into these assemblies with their axes parallel to the monolayer
surface and the whole lipid/peptide complex was submitted to a few steps of simulated annealing and further energy minimisation
techniques in order to equilibrate alkyl chains in the vicinity of the peptide. These simulations yield an estimation of the
penetration depth for the peptide in the monolayer of ∼3.2 ?, whereas experimental approaches to this question were not productive.
The modification in the peptide net electrical charge by interchanging Leu in Lys residues in such systems is also examined:
for low-charged peptides the penetration depth increases.
Received: 20 May 1998 / Accepted : 3 September 1998 / Published online: 7 December 1998 相似文献