共查询到20条相似文献,搜索用时 31 毫秒
1.
Roman Efremov Pavel Volynsky Dmitry Nolde Gérard Vergoten Alexander Arseniev 《Theoretical chemistry accounts》2001,106(1-2):48-54
A heterogeneous implicit membrane-mimetic model is applied to simulations of membrane proteins. The model employs atomic
solvation parameters for gas–water and gas–cyclohexane transfer. It is used to analyze structure, energetics, and orientation
with respect to the bilayer of two polypeptides with different modes of membrane binding – hydrophobic segment of human glycophorin
A (GpA) and cytotoxin II from Naja naja oxiana snake venom (CTX). The native state of GpA represents a transmembrane (TM) α helix, while CTX is a water-soluble protein,
which is able to interact with the cell membrane. The conformational space of the polypeptides was explored in Monte Carlo
simulations. The results show that the most stable conformers of GpA represent a TM α helix. They are additionally stabilized
by an applied TM voltage. The results also show that CTX inserts with its three loops, does not cross the hydrophobic layer,
and stays partially immersed in the membrane. This agrees well with the experimental data, thus confirming the validity of
the solvation model.
Received: 13 June 2000 / Accepted: 15 September 2000 / Published online: 19 January 2001 相似文献
2.
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
3.
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
4.
Christian Bartels Michael Schaefer Martin Karplus 《Theoretical chemistry accounts》1999,101(1-3):62-66
Adaptive umbrella sampling of the potential energy is used as a search method to determine the structures and thermodynamics
of peptides in solution. It leads to uniform sampling of the potential energy, so as to combine sampling of low-energy conformations
that dominate the properties of the system at room temperature with sampling of high-energy conformations that are important
for transitions between different minima. A modification of the procedure for updating the umbrella potential is introduced
to increase the number of transitions between folded and unfolded conformations. The method does not depend on assumptions
about the geometry of the native state. Two peptides with 12 and 13 residues, respectively, are studied using the CHARMM polar-hydrogen
energy function and the analytical continuum solvent potential for treatment of solvation. In the original adaptive umbrella
sampling simulations of the two peptides, two and six transitions occur between folded and unfolded conformations, respectively,
over a simulation time of 10 ns. The modification increases the number of transitions to 6 and 12, respectively, in the same
simulation time. The precision of estimates of the average effective energy of the system as a function of temperature and
of the contributions to the average effective energy of folded conformations obtained with the adaptive methods is discussed.
Received: 11 July 1998 / Accepted: 22 September 1998 / Published online: 17 December 1998 相似文献
5.
Roman G. Efremov Pavel E. Volynsky Manuel A. M. Dauchez Dmitry E. Nolde Alexander S. Arseniev Alain J. P. Alix 《Theoretical chemistry accounts》2001,106(1-2):55-61
Elafin, a specific inhibitor of elastase, is thought to play a regulatory role in inflammation. An NMR-derived solution structure
of recombinant elafin has been reported [Francart et al. (1997) J Mol Biol 268:666 ], although the conformation of its flexible N-terminal part is not established. There is experimental evidence that
the N terminus (residues 1–15) of elafin interacts with the cell membrane. To explore the conformational preferences of residues
in this region, we have performed Monte Carlo simulations of the peptide in water, in cyclohexane, and in a model membrane.
Additionally, 3.7-ns molecular dynamics with explicit water was carried out. The main results were that the hydrophobic environment
stabilizes an α helix in the region 6–11, the peptide is unordered in water, and it is attached to the membrane via the amphiphilic
α-helix 6–11, which inserts with its N terminus forming an angle of about 60° to the membrane plane. We therefore assume that
in nonpolar media the N-terminal part of elafin forms a short α helix which might act as a membrane anchor.
Received: 5 July 2000 / Accepted: 4 October 2000 / Published online: 28 February 2001 相似文献
6.
Michael Schaefer Christian Bartels Martin Karplus 《Theoretical chemistry accounts》1999,101(1-3):194-204
To compare different implicit solvent potentials, the folding thermodynamics of the helical peptide RN24 and the β-hairpin
peptide BH8 are studied by molecular dynamics simulation with adaptive umbrella sampling. As the potential energy functions,
the analytical continuum solvent (ACS) potential and three simplified variants, termed EPSR1, EPSR4, and EPSR10, are used. The ACS potential is a combination of the standard CHARMM force field for the internal energy (bonds, angles,
dihedrals) and the van der Waals energy with the analytical continuum electrostatic (ACE) potential and a non-polar solvation
potential. The EPSR potentials differ from the ACS potential by the use of Coulomb's law with a distance-dependent dielectric
function to calculate the electrostatic energy. With the ACS potential, quantitative agreement with experiment is obtained
for the helix propensity (RN24: 62% calculated vs 50–60% experiment) and the β-hairpin propensity (BH8: 33% calculated vs
19–37% experiment) of the peptides. During the simulations with the EPSR potentials, no significant formation of secondary
structure is observed. It is shown that the preference for coil conformations over conformations with secondary structure
by the EPSR potentials is due to an overestimation of the energy of salt bridge formation, independent of the magnitude of
the Coulomb energy relative to the other energy terms. Possible improvements of the distance-dependent dielectric functions
which may permit their application to the simulation of peptide folding, are discussed.
Received: 11 July 1998 / Accepted: 22 September 1998 / Published online: 17 December 1998 相似文献
7.
H. O. Bertrand A. Pullman K. Zakrzewska B. Hartmann S. Fermandjian 《Theoretical chemistry accounts》1999,101(4):269-273
Phosphorothioate DNAs, have emerged as a new class of potent drugs. They are obtained by the replacement of the anionic oxygens
of the phophodiester backbone by sulphur. A set of parameters has been developed for the FLEX force field implemented in JUMNA
10.0 to take into account the influence of sulphur on the structure of the DNA double helix. The consistency of our parameters
was tested by modelling a phosphorothioate oligomer namely d(GC)8. d(GC)8. Results, obtained on both R-pS and S-pS diastereoisomers, were compared to the phosphodiester counterpart and are in agreement with available experimental data.
Thus, our set of parameters seems suitable for further molecular modelling of other phosphorothioate oligomers.
Received: 15 July 1998 / Accepted: 8 September 1998 / Published online: 10 December 1998 相似文献
8.
M. Micov L. Turi Nagy D. Tunega M. Liška P. Perichta 《Theoretical chemistry accounts》1998,99(6):378-383
A method of solvation energy computation is proposed for ions and molecules in the environment of an ionic melt, based on
the approximation of the ionic melt as an ideal conductor. The method is used to compute equilibrium constants of some equilibria
in cryolite melt. Theoretically obtained results predict that aluminium is bound in tetrafluorocomplexes AlF4
−.
Received: 16 March 1998 / Accepted: 19 June 1998 / Published online: 7 October 1998 相似文献
9.
Adam Liwo Jarosław Pillardy Rajmund Kaźmierkiewicz Ryszard J. Wawak Małgorzata Groth Cezary Czaplewski Stanisaw Ołdziej Harold A. Scheraga 《Theoretical chemistry accounts》1999,101(1-3):16-20
A united-residue model of polypeptide chains developed in our laboratories with united side-chains and united peptide groups
as interaction sites is presented. The model is designed to work in continuous space; hence efficient global-optimization
methods can be applied. In this work, we adopted the distance-scaling method that is based on continuous deformation of the original
rugged energy hypersurface to obtain a smoothed surface. The method has been applied successfully to predict the structures
of simple motifs, such as the three-helix bundle structure of the 10-58 fragment of staphylococcal protein A in de novo folding
simulations and more complicated motifs in inverse-folding simulations.
Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998 相似文献
10.
A sequence-ordered, periodic copolymer of ethylene, ethylene, and acrylic acid, poly (ethylene-per-ethylene-per-acrylic acid) (PEEA), with M
w=1.44×105 has been synthesized by alternating copolymerization of 1,3-butadiene and methyl acrylate, followed by hydrogenation and
hydrolysis. Aqueous solution and dissociation properties of the alkali-soluble PEEA were explored by potentiometric titration
and intrinsic viscosity at 25 °C. The pH values of PEEA were almost constant (pH = 6.48 ∼ 6.55) with an increasing degree
of dissociation (α) from 0.3 to 0.8 at C
s=50 mN NaCl. Correspondingly, the plots of negative logarithm of apparent dissociation constant (pK
a) against α showed a reversed S-shape curve over the whole α, indicating an extensive precipitation and subsequent tran-sition
from compact to coiled conformation. The intrinsic viscosity steeply increased with α above 0.4 up to 9.97 dl/g at α = 1.0.
Good agreement between the observed electrostatic potential and that calculated from the rod model with a smeared charge density
was observed in the region of α higher than 0.9. The dissociation and dissolution processes of PEEA with neutralization in
water were described.
Received: 14 April 1998 Accepted: 3 June 1998 相似文献
11.
Jiabo Li Tianhai Zhu Gregory D. Hawkins Paul Winget Daniel A. Liotard Christopher J. Cramer Donald G. Truhlar 《Theoretical chemistry accounts》1999,103(1):9-63
We present eight new parameterizations of the SM5.42R solvation model: in particular we present parameterizations for HF/MIDI!,
HF/6-31G*, HF/6-31+G*, HF/cc-pVDZ, AM1, PM3, BPW91/MIDI!, and B3LYP/MIDI!. Two of the new cases are parameterized using the reaction-field operator
presented previously, and six of the new cases are parameterized with a simplified reaction-field operator; results obtained
by the two methods are compared for selected examples. For a training set of 2135 data for 275 neutral solutes containing
H, C, N, O, F, S, P, Cl, Br, and I in 91 solvents (water and 90 nonaqueous solvents), seven of the eight new parameterizations
give mean unsigned errors in the range 0.43–0.46 kcal/mol, and the eighth – for a basis set containing diffuse functions –
gives a mean unsigned error of 0.53 kcal/mol. The mean unsigned error for 49 ionic solutes (containing the same elements)
in water is 3.5–3.9 kcal/mol for the Hartree–Fock, Becke–Perdew–Wang-1991 and Becke three-parameter Lee–Yang–Parr cases and
4.1 and 4.0 kcal/mol for parameterized model 3 and Austin model 1, respectively. The methods are tested for sensitivity of
solvation free energies to geometry and for predicting partition coefficients of carbonates, which were not included in the
training set.
Received: 24 November 1998 / Accepted: 31 December 1998 / Published online: 7 June 1999 相似文献
12.
Kishani M. Ranatunga Charlotte Adcock Ian D. Kerr Graham R. Smith Mark S. P. Sansom 《Theoretical chemistry accounts》1999,101(1-3):97-102
The Poisson-Boltzmann equation was solved numerically for models of the pore regions of the Shaker K+ channel and of two glycoporins (LamB and ScrY) to yield electrostatic potential profiles along the pore axes. From these
potential profiles, single-channel current-voltage (I–V) relations were calculated. The importance of a proper treatment of the ionisation state of two rings of aspartate sidechains
at the mouth of the K+ channel pore emerged from such calculations. The calculated most likely state, in which only two of the eight aspartate sidechains
were deprotonated, yielded better agreement with experimental conductance data. An approximate calculation of single-channel
conductances based simply on pore geometry yielded very similar conductance values for the two glycoporins. This differed
from an␣experimentally determined conductance ratio of ScrY:LamB=10:1. Preliminary electrostatics calculations appeared to
reproduce the observed difference in conductance between the two glycoporins, confirming that single-channel conductance is
determined by electrostatic as well as geometric considerations.
Received: 25 May 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998 相似文献
13.
Roman G. Efremov Gérard Vergoten Alexander S. Arseniev 《Theoretical chemistry accounts》1999,101(1-3):73-76
We present a “hydrophobic template” method enabling recognition of α-helix bundles in membrane channels from sequence analysis.
Inspection of hydrophobic properties of pore-forming helices in proteins with known structure (A-B5 toxins) permits delineation of a common polarity motif: two hydrophobic surface stretches separated by polar areas. The bundles
are stabilized by nonpolar interhelical contacts. A number of transmembrane segments were checked for presence of this motif,
and it was detected for pore-forming helices of several ion transporters (segments M2 of acetylcholine and GABAA receptors, α5 peptide of δ-endotoxin), which reveal five α-helix bundle architecture. Applications of the method to modeling
of membrane channels are discussed.
Received: 24 April 1998 / Accepted: 3 September 1998 / Published online: 7 December 1998 相似文献
14.
The conductor-like screening model (COSMO) of solvation has been implemented in the Amsterdam density functional program
with maximum flexibility in mind. Four cavity definitions have been incorporated. Several iterative schemes have been tested
for solving the COSMO equations. The biconjugate gradient method proves to be both robust and memory-conserving. The interaction
between the surface charges and the electron density may be calculated by integrating over either the fitted or exact density,
or by calculating the molecular potential. A disk-smearing algorithm is applied in the former case to avoid singularities.
Several self-consistent field/COSMO coupling schemes were examined in an attempt to reduce computational effort. A gradient-preserving
algorithm for removing outlying charge has been implemented. Preliminary optimized radii are given. Applications to the benzene
oxide-oxepin valence tautomerization and to glycine conformation are presented.
Received: 13 November 1998 / Accepted: 16 December 1998 / Published online: 16 March 1999 相似文献
15.
Gerald Löffler 《Theoretical chemistry accounts》1999,101(1-3):163-169
We performed a very long molecular dynamics simulation of a peptide in explicit water molecules and ions and averaged the
electrostatic potential caused by peptide, water and ions at eight points in the vicinity of the peptide. These electrostatic
potential values were directly compared to the potential calculated by solving the non-linear Poisson-Boltzmann equation for
the system, which describes the solvent using continuum electrostatics. We analyze the contribution of dielectric constant,
conformational flexibility and solvation effects on the electrostatic potential at these eight points.
Received: 24 April 1998 / Accepted: 4 August 1998 / Published online: 23 November 1998 相似文献
16.
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
17.
High-resolution energy spectra of electrons released in Penning ionization collisions of metastable rare gas atoms Rg*(ns) (Rg = He, Ne, Ar, Kr, Xe) with several open-shell and closed-shell atoms are analyzed to determine the well depth of the
potential energy curve which describes the respective autoionizing collision complex. We thereby elucidate trends in the chemical
interaction of Rg* with closed-shell target atoms A(ns
2) and establish a basis for detailed comparison with the respective interactions involving open-shell, ground state alkali
atoms A(ns). From electron energy spectra due to␣associative ionization (RgH+ formation) in Rg* + H(1s) collisions, we determine binding energies for the RgH+(1Σ) ground state potential (Rg = Ne, Ar, Kr, Xe) with uncertainties around 0.03 eV.
Received: 30 June 1998 / Accepted: 5 August 1998 / Published online: 28 October 1998 相似文献
18.
The prediction of the 13C NMR signals for derivatives of naphthalene has been investigated using mathematical modeling techniques. Two empirical multiple
regression models which utilize the field, resonance, and Charton's steric parameters together with molar refractivity were
developed, one for α- and the other for β-substituted naphthalene derivatives. In the α case the model had a correlation coefficient
of observed versus predicted line positions of r = 0.973 with a standard deviation of 2.2 ppm while in the β case r = 0.979 with the standard deviation being 2.3 ppm. The database consisted of 3152 signals from 394 naphthalene derivatives.
We also report the use of the Taft steric parameter in place of the Charton steric parameter in the above- mentioned prediction
equations.
Received: 19 June 1998 / Accepted: 20 October 1998 / Published online: 16 March 1999 相似文献
19.
Kazunari Naka Hirofumi Sato Akihiro Morita Fumio Hirata Shigeki Kato 《Theoretical chemistry accounts》1999,102(1-6):165-169
The free-energy profile for the Menshutkin-type reaction NH3 + CH3Cl → NH3CH3
+ + Cl− in aqueous solution is studied using the RISM-SCF method. The effect of electron correlation on the free-energy profile is
estimated by the RISM-MP2 method at the HF optimized geometries along the reaction coordinate. Solvation was found to have
a large influence on the vibrational frequencies at the reactant, transition state and product; these vibrational frequencies
are utilized to calculate the zero-point energy correction of the free-energy profile. The computed barrier height and reaction
exothermicity are in reasonable agreement with those of experiment and previous calculations. The change of solvation structure
along the reaction path is represented by radial distribution functions between solute-solvent atomic sites. The mechanisms
of the reaction are discussed from the view points of solute electronic and solvation structures.
Received: 26 June 1998/Accepted: 28 August 1998 / Published online: 2 November 1998 相似文献
20.
Interest in the transmembrane receptors tyrosine kinase of the erbB family is high due to the involvement of some of the
members in human cancers. The original oncogenic alleles of neu discovered in rat neuroectodermal tumors lead to single Val664Glu
substitution within the predicted transmembrane domain. Identical substitution at the homologous position 659 constitutively
activates the oncogenic potential of the human ErbB-2 receptor by enhanced receptor dimer formation. The precise molecular
details of receptor dimerization are still unknown and to acquire more knowledge of the mechanisms involved, molecular dynamics
simulations are undertaken to study transmembrane dimer association. Transmembrane helices are predicted to associate in left-handed
coiled-coil structures stabilized by Glu-Glu interhelix hydrogen bonds in the mutated form. The internal dynamics reveals
π helix deformations which modify the helix-helix interface. Predicted models agree with those suggested from polarized IR
and magic-angle spinning NMR spectroscopy.
Received: 24 April 1998 / Accepted: 17 September 1998 / Published online: 10 December 1998 相似文献