摘要:

AbstractThe quadratic nonlinear optical susceptibility of a solution of helical polymers and of samples with helices oriented parallel to each other is calculated for regions of characteristic vibrations and of their overtones. The important role of electrooptical and of mechanical anharmonicity for exhibition of overtones in nonlinear spectroscopy is shown. The possibility of the appearance of the giant polarizabilities near bound overtone states is analyzed. The overtone spectrum of amide I is modeled numerically. © 1994 John Wiley&Sons, Inc

ISSN:0006-3525    

DOI:10.1002/bip.360340702

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe Helmholtz free energyF(rather than the energy) is the correct criterion for stability; therefore, calculation ofFis important for peptides and proteins that can populate a large number of metastable states. The local states (LS) method proposed by H. Meirovitch [(1977)Chemical Physics Letters, Vol. 45, p. 389] enables one to obtain upper and lower bounds of the conformational free energy,FB(b,l) andFA(b,l), respectively, from molecular dynamics (MD) or Monte Carlo samples. The correlation parameterbis the number of consecutive dihedral or valence angles along the chain that are taken into account explicitly. The continuum angles are approximated by a discretization parameterl; the larger arebandl, the better the approximations; whileFAcan be estimated efficiently, it is more difficult to estimateFB. The method is further developed here by applying it to MD trajectories of a relatively large molecule (188 atoms), the potent “Asp4‐Dpr10” antagonist [cyclo(4/10)‐(Ac‐Δ3Pro1‐D‐pFPhe2‐D‐Trp3‐Asp4‐Tyr‐5‐D‐Nal6‐Leu7‐Arg8‐Pro9‐Dpr10‐NH2)] of gonadotropin releasing hormone (GnRH). The molecule was simulated in vacuo atT= 300 K in two conformational states, previously investigated [J. Rizo et al.Journal of the American Chemical Society, (1992) Vol. 114, p. 2860], which differ by the orientation of the N‐terminal tail, above (tail up, TU) and below (tail down. TD) the cyclic heptapeptide ring. As in previous applications of the LS method, we have found the following: (1) WhileFAis a crude approximation for the correctF, results for the difference, ΔFA=FA(TD) –FA(TU) converge rapidly to 5.6(1) kcal/mole as the approximation is improved (i.e., asbandlare increased), which suggests that this is the correct value for ΔF; therefore TD is more stable than TU. (The corresponding difference in entrophy.TΔSA= 1.3(2) kcal/mole, is equal to the value obtained by the harmonic approximation.) (2) The lowest approximation, which has the minimal number of local states, i.e., based onb= 0 (no correlations) andl= 1 (the angle values are distributed homogeneously), also leads to the correct value of ΔF, within the error bars. This is important since the lowest approximation can be applied even to large proteins. (3) The method enables one to define the entropy of a part of the molecule and thus to measure the flexibility of this part. We have verified that the results forT[SA(TU) –SA(TD)] of the tail alone converged to 2.4(1) kcal/mole, which demonstrates the relatively high flexibility of the tail in the TU state. In order to study the random coil state, the Asp4‐Dpr10analogue and its linear version were simulated by MU at 1000 K. We have been able to calculate a lower bound, ∼ 25 kcal/mole forT[S(linear) –S(cyclic)], which is the reduction in the conformational entropy c

ISSN:0006-3525    

DOI:10.1002/bip.360340703

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

年代:1994

数据来源: WILEY

摘要:

AbstractA quantum mechanical study to compare the ability of α‐aminoisobutyric acid (Aib), de‐hydroalanine (ΔAla), and alanine (Ala) residues to stabilize helical conformations has been performed. To address the study, the oligopeptides Xn(X = Aib, ΔAla and Ala), wherenvaries from 1 to 6, were computed with the AM1 semiempirical method. The results show that the residues modified at the Cαcarbon atom, Aib and ΔAla, are better helical formers than Ala. Thus, a cooperative energy effect was found for both residues, and especially for ΔAla. These terms permit the understanding the different conformational behaviors between Ala and its Cα‐modified residues Aib and ΔAla. This trend is important for de novo protein design, where Aib and ΔAla must be considered useful residues in the design of synthetic helical motifs. © 1994 John

ISSN:0006-3525    

DOI:10.1002/bip.360340704

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

年代:1994

数据来源: WILEY

摘要:

AbstractA rigorous theory is developed for ethidium binding to linear and circular DNAs and for the ratios of topoisomers produced upon ligation of an equilibrium population of noncovalently closed circles in the presence of ethidium. Assuming an unwinding angle ϕE= 26° for intercalated ethidium, optimum values of the intrinsic binding constant,KE= 7.16 × 104M−1, the intrinsic twist,l0= 23.746 turns, and twist energy parameter,Et= 5250, are obtained by fitting the present theory to the data of Shore and Baldwin [(1993)Journal of Molecular Biology, Vol. 170, pp. 983–1007] for a 247 base pair DNA. A very good fit is achieved with these optimum values, but a poor fit results when the parameters estimated by Shore and Baldwin are employed in the same theory. Three assumptions employed in the analysis of Shore and Baldwin are found to be not strictly valid. Adoption of the present substantially largerEtvalue as representative of their short DNAs would allow theEtvsNdata of Shore and Baldwin to conform to the shape predicted by Shimada Yamakawa [(1985)Journal of Molecular Biology, Vol. 184, pp. 319–329] and Frank‐Kamenetskii et al. [(1985)Journal of Biomolecular Structure and Dynamics, Vol. 2, pp. 1005–1012], and would imply thatallof their DNAs exist in a substantially stiffer than normal state. © 1994 John Wi

ISSN:0006-3525    

DOI:10.1002/bip.360340705

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

年代:1994

数据来源: WILEY

摘要:

AbstractCD and nmr studies have been carried out on aqueous trifluoroethanol (TFE) solutions of bradykinin (BK) and a bradykinin antagonist. The CD results exhibit a striking effect of TFE on the spectra of BK, with sequence Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe‐Arg, and the BK antagonist, with sequenceD‐Arg‐Arg‐Pro‐Hyp‐Gly‐Thi‐D‐Ser‐D‐Cpg‐Cpg‐Arg [where Hyp is 4‐hydroxy‐L‐proline; Thi refers to β‐(2‐thienyl)‐L‐alanine and Cpg refers to α‐cyclopentylglycine]. The effect of increasing concentration of TFE in water on the difference ellipticity at 222 nm was examined and showed that BK may be a mixture of at least two different conformers, one of which largely forms when the TFE concentration is increased beyond 80%. The linear extrapolation of 100% of the difference ellipticity of BK at low TFE concentrations yields a value in agreement with that shown by the BK antagonist, indicating that the conformation of BK at the lower TFE concentrations is similar to that of the BK antagonist. The conformational analysis was carried out using both one‐dimensional and two‐dimensional1H‐nmr techniques. The total correlation spectroscopy (TOCSY) spectrum of BK in a 60/40% (v/v) TFE/H2O solution at 10°C and a nuclear Overhauser effect spectroscopy (NOESY) spectrum that shows only sequential Hα(i) – NH(i+ 1) or the Hα(i) – Hδδ′(i+ 1) NOEs indicate that the majority of the molecules adopt an all‐transextended conformation. The TOCSY for BK in the 95/5% (v/v) TFE/H2O solution shows that there are two major conformations in the solution with about equal population. The NOESY experiment shows two new important cross peaks for one conformation, namely Pro2(α)‐Pro3(α) and the Pro2(α)‐Gly4(NH), indicating acisPro2‐Pro3bond and a type VI β‐turn between residues Arg1and Gly4involvingcisproline at position 3, respectively. The low temperature coefficient of Gly4for this conformation suggests the presence of an intramolecular hydrogen bond, therefore a type VIa β‐turn is present. The other conformation is alltransand extended.The BK antafonist shows difference CD spectra in TFE solutions referred to H2O that are superficially indicative of a β‐bend. However, nmr speaks against this possibility, as only one set of peaks were observed in the TOCSY and NOESY experiments, indicating an all‐transextended confirmation over the range of TFE concentrations. The BK‐antagonist CD data suggest that solvent perturbation of the CD of an extended confirmation perturbation of the optical activity of the thienyl moiety of the peptide since the CD spectrum of N‐acetyl‐β‐thienyl‐L‐alanine N‐methylamide is strongly perturbed by TFE. The p

ISSN:0006-3525    

DOI:10.1002/bip.360340706

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

年代:1994

数据来源: WILEY

摘要:

AbstractThe conformation of basic fatty acid binding protein from chicken liver and the binding properties of theapoprotein toward 11‐dansylamino‐undecanoic acid were investigated by CD and fluorescence spectroscopy. In one set of experiments the binding process was followed by the appearance of induced optical activity in the absorption region of the dansyl chromophore. In a second set of experiments the binding process was followed by the large enhancement of emission fluorescence of the dansyl fluorophore. From the saturation curves, the stoichiometry of the complex and the binding constant of the fatty acid to the protein were precisely determined. The values of the dissociation constant determined with the two methods were in excellent agreement: we obtainedKD= (1.0 ± 0.1) · 10−6Min a 0.9 : 1 stoichiometry. The native conformation of the protein is remarkably stable in a variety of solvent systems, including acetonitrile–water, ethylene glycol–water, and dicxane–water of various compositions. The CD results also showed that the binding of the fatty acid does not induce any appreciable change in the protein conformation. In a mixture of water and 2,2,2‐trifluoroethanol 1 : 9 (v/v), the native conformation collapses and a new ordered structure is formed, characterized by a high amount of α‐helix. © 1994 J

ISSN:0006-3525    

DOI:10.1002/bip.360340707

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

年代:1994

数据来源: WILEY

摘要:

AbstractCommonly a key element enabling proteins to function is an amino acid residue or residues with functional side chains having shifted pKa values. This article reports the results on a set of protein‐based polymers (model proteins) that exhibit hydrophobic folding and assembly transitions, and that have been designed for the purpose of achieving large hydrophobic‐induced pKa shifts by selectively replacing Val residues by Phe residues. The high molecular weight polypentapeptides, actually poly (tricosapeptides) with six varied pentamers in fixed sequence, were designed and synthesized to have the same amino acid compositions but different proximities between a single aspartic acid residue and 5 Phe residues per 30 residues. With the 5 Phe residues distal from the Asp residue, the observed pKa shift was 2.9 when compared to the Val‐containing reference. With the 5 Phe residues within 1 nm of the Asp residue, the pKa shift was 6.2. This represents a free energy of interaction of 8 kcal/moles. To our knowledge, this is the largest pKa shift documented for an Asp residue in a polypeptide– or protein–water system.Data are reviewed that do not support the usual electrostatic arguments for pKa shifts of charge–charge repulsion and/or unfavorable ion self‐energies arising from displacement of water by hydrophobic moieties, but rather the data are interpreted to indicate the presence of an apolar–polar repulsive free energy of hydration, which results from a potentially highly cooperative competition between apolar and polar species for hydration. © 1994 John

ISSN:0006-3525    

DOI:10.1002/bip.360340708

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

年代:1994

数据来源: WILEY

摘要:

AbstractHighly oriented fibers of Li‐, Na‐, K‐, and CsDNA were prepared with a previously developed wet spinning method. The procedure gave a large number of equivalent fiber bundle samples (reference length,L0, typically = 12–15 cm) for systematic measurements of the fiber lengthLin ethanol–water solutions, using a simple mechanochemical set up. The decrease in relative lengthL/L0with increasing ethanol concentration at room temperature gave evidence for the B‐A transition centered at 76% (v/v) ethanol for NaDNA fibers and at 80 and 84% ethanol for K‐ and CsDNA fibers. A smaller decrease inL/L0of LiDNA fibers was attributed to the B‐C transition centered at 80% ethanol. In a second type of experiment with DNA fibers in ethanol–water solutions, the heat‐induced helix–coil transition, or melting, revealed itself in a marked contraction of the DNA fibers. The melting temperatureTm, decreased linearly with increasing ethanol concentration for fibers in the B‐DNA ethanol concentration region. In the B‐A transition region, Na‐ and KDNA fibers showed a local maximum inTm. On further increase of the ethanol concentration, the A‐DXA region followed with an even steeper linear decrease inTm. The dependence on the identity of the counterion is discussed with reference to the model for groove binding of cations in B‐DNA developed by Skuratovskii and co‐workers and to the results from Raman studies of the interhelical bonds in A‐DNA performed by Lindsay and co‐workers. An attempt to apply the theory of Chogovadze and Frank‐Kamenetskii on DNA melting in the B‐A transition region to the curves failed. However, for Na‐ and KDNA theTmdependence in and around the A‐B transition region could be expressed as a weighted mean value ofTmof A‐ and B‐DNA. On further increase of the ethanol concentration, above 84% ethanol for LiDNA and above about 90% ethanol for Na‐, K‐, and CsDNA, a drastic change occurred.Tmincreased and a few percentages higher ethanol concentrations were found to stabilize the DNA fibers so that they did not melt at all, not even at the upper temperature limit of the experiments (∼ 80°C). This is interpreted as being due to the strong aggregation induced by these high ethanol concentrations and to the formation of P‐DNA. Many features of the results are compatible with the counterion–water affinity model. In another series of measurements,Tmof DNA fibers in 75% ethanol was measured at various salt concentrations. No salt effect was observed (with the exception of LiDNA at low salt concentrations). This result is supported by calculations within the Poisson

ISSN:0006-3525    

DOI:10.1002/bip.360340709

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

年代:1994

数据来源: WILEY

摘要:

AbstractA three‐dimensional Hartree–Fock crystal‐orbital calculation on the crystal of diprotonated deoxycytidine‐5′‐monophosphate monohydrate has been carried out using the CRYSTAL92 routine package. According to the calculation, this crystallohydrate can be considered a quasi one‐dimensional hole semiconductor with the indirect fundamental gap of 1.66 eV and with a possibility for the uv‐excited quasi one‐dimensional electron photoconductivity. The physical source for such properties is the charge transfer from the phosphate to the water molecule and cytosine residue, favored by the strong electrostatic interaction between nucleotide zwitterions and by the formation of the infinite spirals of hydrogen‐bonded zwitterions along one of the crystallographic axes. © 1994

ISSN:0006-3525    

DOI:10.1002/bip.360340710

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

年代:1994

数据来源: WILEY

摘要:

AbstractA matching algorithm using surface complementarity between receptor and ligand protein molecules is outlined. The molecular surfaces are represented by “critical points,” describing holes and knobs. Holes (maxima of a shape function) are matched with knobs (minima). This simple and appealing surface representation has been previously described by Connolly [(1986)Biopolymers, Vol. 25, pp. 1229–1247]. However, attempts to implement this description in a docking scheme have been unsuccessful (e.g., Connolly, ibid.). In order to decrease the combinatorial complexity, and to make the execution time affordable, four critical hole/knob point matches were sought. This approach failed since some bound interfaces are relatively flat and do not possess four critical point matches. On the other hand, matchings of fewer critical points require a very time‐consuming, full conformational (grid) space search [Wang, (1991)Journal of Computational Chemistry, Vol. 12, pp. 746–750]. Here we show that despite the initial failure of this approach, with a simple and straightforward modification in the matching algorithm, this surface representation works well. Out of the 16 protein‐protein complexes we have tried, 15 were successfully docked, including two immunoglobulins. The entire molecular surfaces were considered, with absolutely no additional information regarding the binding sites. The whole process is completely automated, with no manual intervention, either in the input atomic coordinate data, or in the matching. We have been able to reach this level of performance with the hole/knob surface description by using pairs of critical points along with their surface normals in the calculation of the transformation matrix. The success of this approach suggests that future docking methods should use geometric docking as the first screening filter. As a geometrically based docking methodology predicts correct, along with incorrect, receptor‐ligand bound conformations, all solutions need to undergo energy screening to differentiate between them. © 1994 John W

ISSN:0006-3525    

DOI:10.1002/bip.360340711

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

年代:1994

数据来源: WILEY