摘要:

AbstractA winter flounder antifreeze polypeptide (HPLC‐6) has been studied in vacuo and in aqueous solution using molecular dynamics computer simulation techniques. The helical conformation of this polypeptide was found to be stable both in vacuum and in solution. The major stabilizing interactions were found to be the main‐chain hydrogen bonds, a salt‐bridge interaction, and solute–solvent hydrogen bonds. A significant bending in the middle of the polypeptide chain was observed both in vacuo and in solvent at 300 K. Possible causes of the bending are discussed. From simulations of mutant polypeptide molecules in vacuo, it is concluded that the bend in the native polypeptide was caused by side chain to backbone hydrogen bond competition involving the Thr 24 side chain and facilitated by strains on the helix resulting from the Lys 18‐Glu 22 salt bridge. © 1993 John Wiley

ISSN:0006-3525    

DOI:10.1002/bip.360331002

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractSpirobenzopyran units were bound to the side chains of poly (L‐glutamic acid) and partially methylated poly(L‐glutamate)s. The modified polymers were found to exhibit “reverse photochromism” in hexafluoro‐2‐propanol (HFP), so the samples kept in the dark were characterized by an intense absorption band in the visible range of the spectrum, which was completely erased upon exposure to sunlight or irradiation at 500–550 nm.The CD spectra showed that the macromolecules adopted a random coil conformation in the dark, whereas the bleached solutions after exposure to light displayed the typical CD pattern of the α‐helix. The back reaction in the dark was accompanied by the progressive decrease of the helix content and recovery of the original disordered conformation. The photoinduced conformational changes resulted in large and reversible viscosity variations.When spiropyran side chains were converted to “spiropyran salts” of trifluoroacetic acid, the system was still photochromic, but the macromolecules were disordered both in the dark and light conditions. However, when appropriate amounts of methanol were added as a cosolvent to the HFP solutions, the system responded to light, giving reversible variations of the α‐helix content. Irradiation at appropriate solvent compositions allowed modulation of the extent of the photoresponse. © 1

ISSN:0006-3525    

DOI:10.1002/bip.360331003

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA quantitative understanding of helix–coil dynamics will help explain their role in protein folding and in folded proteins. As a contribution to the understanding, the equilibrium and dynamical aspects of the helix–coil transition in polyvaline have been studied by computer simulation using a simplified model of the polypeptide chain. Each amino acid residue is treated as a single quasiparticle in an effective potential that approximates the potential of mean force in solution. The equilibrium properties examined include the helix–coil transition and its dependence on chain position and well depth at the coil–helix interface. A stochastic simulation of the Brownian motion of the chain in its solvent surroundings has been used to investigate dynamical properties. Time histories of the dihedral angles have been used to study the behavior of the helical structure. Auto and cross‐correlation functions have been calculated from the time histories and from the state (helix or coil) functions of the residues with relaxation times of tens to hundreds of picoseconds. Helix–coil rate constants of tens of ns−1were found for both directions of the transition. © 1993 John W

ISSN:0006-3525    

DOI:10.1002/bip.360331004

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe program AMBER 3.0 has been used to generate molecular dynamics trajectories of a poly (dA)·poly (dT) decamer. The simulations were performed using different methods to treat solvent effects. Results of a simulation including 18 counterions NH +4and 4109 water molecules under (N, P, T) conditions were compared to simulation runs with implicit solvent representation in which solvent screening effects were represented by the use of a sigmoidal distance‐dependent dielectric function. In the latter case, the system was simulated under microcanonical (N, V, E) and canonical (N, V, T) conditions. For the fully hydrated system simulation, a preequilibration protocol was developed since it was observed that long and progressive periods of heating and equilibration on the overall system were necessary in order to avoid energetic collisions between the solute and the solvent molecules, leading to severe irreversible deformation of the solute. A detailed analysis of DNA conformations, sugar puckers, and stability of the hydrogen bonds, Watson–Crick and three‐center H bonds, is reported. The results show that DNA remains essentially in the B conformer with a tendency in the hydrated model to adopt a slightly distorted, unwound, and stretched conformation in comparison to standard B‐DNA. Concerning sugar puckers, the mean pseudorotation phases of the adenine residues are systematically higher than those of the thymine residues, except in the case of the hydrated model for which a particular behavior is observed for the adenine strand. In this case, the terminal bases oscillate between C2′,‐endoand O4′,‐endoand the central ones stay in the C3′,‐endodomain. The mean lifetimes of the internal Watson–Crick H‐bond (A)HN6O4(T) are also dependent on the base pairs included in the calculation, excepted for the implicit solvent simulation at constant temperature. The three‐center H bonds have very small mean lifetimes in all three cases of MD simulation. In the minor groove of the hydrated model, a spine of hydration is found as observed by x‐ray crystallography and other theoretical simulations. On the basis of the rms deviations, it appears that the fully hydrated simulation has not reached a plateau at the end of the run, while the implicit simulation at constant energy seems to have converged. At constant temperature, very large oscillations in rms deviations are obser

ISSN:0006-3525    

DOI:10.1002/bip.360331005

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractAqueous solutions formed by polypeptides, simple models of proteins, and bile salts (sodium cholate and deoxycholate, NaC and NaDC, respectively) or bilirubin‐IXα (BR) have been studied by CD measurements. They could mimic more complicated biliary systems, thus supplying a possible interpretation of the behavior of some amino acid residues in the biliary proteins. The aggregation of NaDC and NaC in water can be monitored by CD measurements. Bile salts, in submicellar and micellar form, stabilize poly (L‐Lys) (PLL) in α‐helical conformation. The α‐helix content increases with increasing bile salt concentration and ionic strength. NaDC seems to be a slightly better stabilizing agent of the α‐helix conformation than NaC. Models characterized by hydrogen bonds between bile salts and PLL are proposed, also resorting to previous data available on the systems formed by NaDC and poly(L‐Leu‐L‐Leu‐L‐Lys) (PLLL) or poly(L‐Leu‐L‐Leu‐L‐Asp) (PLLA). Binding of BR to PLL, poly(D‐Lys), poly(L‐Glu), PLLL, and PLLA in water has been investigated by CD spectra in order to clarify the nature of the association complexes and the mechanism of the BR enantioselective complexation. Potential energy calculations provide binding models capable of explaining the enantioselective ability of the PLL and PLLL α‐helices toward the left‐ and right‐handed enantiomer of BR, respectively. BR is bound to ‐NH2groups of PLL and PLLL lying on a right‐ and left‐handed spiral, respectively. These results, together with those formerly obtained for some bile salts–BR systems, indicate that the selectivity originates from a binding that involves large regions of the BR molecule and gives rise, very probably, to moderate conformational changes from the “ridge tile” structure observed in the crystals. In some cases van der Waals forces can play a crucial role in the chiral recognition of bilirubin. Moreover, possible interaction models of BR with human serum albumin are proposed on the basis of a recent x‐ray cry

ISSN:0006-3525    

DOI:10.1002/bip.360331006

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractWe have carried out a nanosecond molecular dynamics simulation of an analogue of the ribonuclease C‐peptide in water. The overall conformation has an extended region for the first three amino acids connected to an α‐helix for residues 4–13, and this basic structure is preserved throughout the simulation, with helical hydrogen bonds present 87% of the time, on average. The final helical hydrogen bond is spontaneously broken and re‐formed several times, providing a detailed picture of such winding/unwinding events. The simulation was used to estimate the effects of internal motion on proton nuclear Overhauser effect spectroscopy (NOESY) intensities for several classes of important cross peaks. Within the helical regions, the effects of internal motion vary only a little from one residue to another for backbone–backbone cross peaks, and the relevant correlation functions reach plateau values within about 50 ps. The spectral simulations show, however, that it may be difficult to establish a close quantitative connection between NOESY cross‐peak volumes and measures of helical content. © 1993 John Wi

ISSN:0006-3525    

DOI:10.1002/bip.360331007

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe13C off‐resonance rotating frame spin–lattice relaxation technique is applicable to the study of protein rotational diffusion behavior in a variety of experimental situations. The original formalism of James and co‐workers (1978) (J. Am. Chem. Soc.Vol. 100, pp. 3590–3594) incorporated random isotropic reorientational motion of a rigid spherical rotor with no provision for backbone or side‐chain carbonyl group internal motion. Here we demonstrate that the failure to include such internal motion may lead to erroneous rotational correlation time determinations for overall reorientational motion. The effect becomes severe for protein molecular masses in excess of 100 kD. Inclusion of both backbone and side‐chain carbonyl carbon internal motion, using reasonable parameters derived from the literature [R. Levy and M. Karplus (1979),Chemical Physics Letters, Vol. 65, pp. 4–11; G. Careri, P. Fasella, and E. Gratton (1975),Critical Reviews in Biochemistry, Vol. 3, pp. 141–164; G. Lipari, A. Szabo, and R. Levy (1982),Nature, Vol. 300, pp. 197–198], plus corrections for anisotropic tumbling [C. F. Morgan, T. Schleich, G. H. Caines, and D. Michael (1990),Biopolymers, Vol. 29, pp. 469–480] and microscopic viscosity [S. H. Koenig (1980),ACS Symposium. Series, Vol. 127, pp. 157–176], leads to reliable values for the correlation time describing overall protein reorientation up to molecular masses of approximately 1000 kD. © 199

ISSN:0006-3525    

DOI:10.1002/bip.360331008

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe energetics of the χ 12χ3χ 22portion of the disulfide bridge have been obtained from an ab initio study of diethyl disulfide. Calculations at the 3‐21G* level were done on relaxed structures at every ∼ 30° in χ 12and χ 22, and the additional energies for small Δχ3were obtained. CompleteE(χ 12, χ 22) and χ 03(χ 12, χ 22) maps were computed from Fourier series expansions. These results have been used to calculate the energetics of 92 disulfide bridges in known protein structures, and to compare ab initio and molecular mechanics energies for some observed and predicted bridges. The differences found in relative energies and in χ 03values suggest that present energy functions give a limited description of the structural and energetic properties of the disulfid

ISSN:0006-3525    

DOI:10.1002/bip.360331009

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractBased on Lifson–Roig's helix–coil transition theory, substitution of a single heteroresidue into a homopolymer host is studied. This study models recent experiments that substitute a single amino acid into a small peptide in water [A. Chakrabartty, J. A. Schellman, and R. L. Baldwin (1991),Nature, Vol. 351, pp. 586–688]. Our formalism, which is based on a perturbation method, differs from the existing theory for sequenced polymers and is naturally analogous, hence likely to be useful, to substitution experiments in the laboratory. It is shown that the intrinsic helix propensitywis directly proportional to the equilibrium constant for the helix–coil equilibrium of a single residue in a host peptide. This intuitive new result will simplify experimental data interpretations for measurements of the helical conformation on the single amino acid level. It is also shown that substitution affects the total helicity of the host peptide according to two considerations: the helicity of the replaced residue prior to the substitution, and the sensitivity of the site, a measure of neighboring interactions. The relationship between substitution stability and thermal stability is explored. © 1993 John Wiley&S

ISSN:0006-3525    

DOI:10.1002/bip.360331010

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe molecular and crystal structures of one derivative and three homopeptides (from the di‐to the tetrapeptide level) of the chiral, Cα, α‐disubstituted glycine Cα‐methyl, Cα‐benzylglycine [(αMe)Phe], have been determined by x‐ray diffraction. The derivative is mClAc‐D‐(αMe)Phe‐OH, and the peptides arepBrBz‐[D‐(αMe)Phe]2‐NHMe,pBrBz‐[D‐(αMe)Phe]3‐OH hemihydrate, andpBrBz‐[D‐(αMe)Phe]4‐OtBu sesquihydrate. All (αMe)Phe residues prefer ϕ,ψ torsion angles in the helical region of the conformational map. The dipeptide methylamide and the tripeptide carboxylic acid adopt a β‐turn conformation with a 1 ← 4 CO…︁HN intramolecular H bond. The structure of the tripeptide carboxylic acid is further stabilized by a 1 ← 4 CO…︁HO intramolecular H bond, forming an “oxy‐analogue” of a β‐turn. The tetrapeptide ester is folded in a regular (incipient) 310‐helix. In general, the relationship between (αMe)Phe chirality and helix screw sense is opposite to that exhibited by protein amino acids. A comparison is made with the conclusions extracted from published work on

ISSN:0006-3525    

DOI:10.1002/bip.360331011

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY