摘要:

AbstractUsing a factor analysis technique, the experimental physicochemical data on the hydration of mononucleotides, several polynucleotides, their double‐helical complexes and natural DNAs were studied. The information about the factors determining the changes in physicochemical parameters vs the hydration was obtained. This work discusses a possible physical sense of the factors obtained and the expedience of using factor analysis to interpret the molecular‐biophysical experime

ISSN:0006-3525    

DOI:10.1002/bip.360310302

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe effect of basic oligopeptides (Lys‐Ala‐Ala)n(n= 1–5, 10) and (Lys‐Leu‐Ala)n(n= 1–4) on the B‐Z transition of poly (dG‐dC)·poly (dG‐dC) in water–methanol solutions was investigated using CD and uv spectroscopy: In the absence of peptides, the concentration of methanol at the midpoint of the B‐Z transition is 64% at 25°C. The transition is temperature dependent and the B conformation is preferred at higher temperatures.All peptides tested shift the midpoint of the B‐Z transition to lower concentrations of methanol. For shorter peptides this effect increases with an increasing number of monomeric units, showing the importance of the number of positive charges in the peptide molecule. At conditions of low methanol content, the trimer and tetramer of the (Lys‐Leu‐Ala)nseries have a greater effect on the B‐Z transition than the corresponding oligomers of the (Lys‐Ala‐Ala)nseries. This indicates an important influence of the presence of hydrophobic groups in the peptide side chains on the binding.In the presence of peptides, the B‐Z transition is also temperature dependent and the B conformation is preferred at higher temperatures. The addition of peptides results in an increase of the transition midpoint and of the transition width. These parameters were used for the calculation of the transition enthalpy ΔHB‐Zin 65% methanol, which is −1.15 ± 0.25 kcal/base pair. Since the van't Hoff enthalpy ΔHVHcalculated from the temperature dependence of the B‐Z transition in the absence of peptides is −130 kcal/mol, the length of the cooperative unit is about 110 base pairs. The results suggest that the mechanism of Z‐DNA induction is similar but not identical with that involved

ISSN:0006-3525    

DOI:10.1002/bip.360310303

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

年代:1991

数据来源: WILEY

摘要:

AbstractThere has been much interest recently in the structure of small peptides in solution. A recent study by Bradley and co‐workers [(1989) in Techniques of Protein Chemistry, Hugli, T. E., Ed., Academic Press, Orlando, FL, pp. 531–546; (1990)Journal of Molecular Biology, 215, pp. 607–622] describes a 17‐residue peptide that is stable as a monomeric helix in aqueous solution at low pH, as determined by two‐dimensional nmr and CD spectroscopy. They also have determined the helix content of the peptide as a function of pH using CD. We performed molecular dynamics simulations, with an empirical force field, of this peptide at low pH, with three different dielectric models: a linear distance‐dependent dielectric function (ε =R); a modified form [J. Ramstein and R. Lavery (1988)Proceedings of the National Academy of Science, USA, Vol. 85, pp. 7231–7235] of the sigmoidal distance‐dependent dielectric function of Hingerty and co‐workers [(1985)Biopolymers, Vol. 24, pp. 427–439]; and ε = 1 with the peptide immersed in a bath of water molecules. We found that simulations with the sigmoidal dielectric function and the model with explicit water molecules resulted in average distances for particular interactions that were consistent with the experimental nmr results, with the sigmoidal function best representing the data. However, these models exhibited very different helix‐stabilizing interactions. We also performed simulations using the sigmoidal function at moderate and high pH to compare to experimental determinations of the pH dependence of helix content. Helix content did not decrease with increases in pH, as shown experimentally. We did, however, observe changes in a specific side chain–helix dipole interaction that was implicated in determining the pH‐dependent behavior of this peptide. Overall, the sigmoidal dielectric function was a reasonable alternative to adding explicit water molecules. In comparing 100 ps molecular dynamics simulations, the sigmoidal function was much less computer intensive and sampled more of conformational space than the treatment using explicit water molecules. Sampling is especially important for this system since the peptide has been shown experimentally to populate both helical a

ISSN:0006-3525    

DOI:10.1002/bip.360310304

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe interaction of succinyl‐Pro‐Ala, a competitive inhibitor ofAchromobacter iophaguscollagenase, with the enzyme was studied by longitudinal proton and tritium relaxation. Specific deuterium and tritium labeling of the succinyl part at vicinal positions allowed the measurement of the cross‐relaxation rates of individual proton or tritium spin pairs in the inhibitor–enzyme complex as well as in the free inhibitor. Overall correlation times, internuclear distances, and qualitative information on the internal mobility in Suc1(as provided by the generalized order parameterS2) could be deduced by the comparison of proton and tritium cross‐relaxations of spin pairs at complementary positions in the CH2CH2 moiety as analyzed in terms of the model‐free approach by Lipari and Szabo.The conformational and motional parameters of the inhibitor in the free and enzyme‐bound state were directly compared by this method. The measurement of proton cross‐relaxation in the Ala residue provided additional information on the inhibitor binding. The determination of the order parameter in different parts of the inhibitor molecule in the bound state indicates that the succinyl and alanyl residues are primarily involved in the interaction with the enzyme active site. The succinyl moiety, characterized in solution by the conformational equilibrium among the three staggered rotamers–i.e.,trans: 50%;g+: 20%;g−; 30%–adopted in the bound state th

ISSN:0006-3525    

DOI:10.1002/bip.360310305

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe Electrostatically Driven Monte Carlo (EDMC)method was applied in a study of a decamer of glycine whose conformational behavior is described by the Empirical Conformational Energy Program for Peptides (ECEPP/2) potential energy model. When free neutral end groups were used, it was found that conformations that were not α‐helical had significantly lower potential energies than fully α‐helical ones. However, when the N‐ and C‐termini were blocked by acetyl and methyl amide groups, respectively, the number of unsatisfied hydrogen‐bond donors and acceptors at the helix termini was diminished from 8 to 6; in this case, the possibility of forming two additional α‐helical hydrogen bonds was an important enough factor in making the α‐helical conformation the one with the lowest energy. The EDMC method was used as a global energy optimizer since it does not often become trapped in high‐

ISSN:0006-3525    

DOI:10.1002/bip.360310306

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

年代:1991

数据来源: WILEY

摘要:

AbstractThe structures of the complexes formed in aqueous solution between ditercalinium, a bisintercalating drug, and both the self‐complementary tetranucleotide d(GCGC)2and octanucleotided(CCTATAGG)2, have been investigated by 400‐MHz1H‐nmr and 162‐MHz31P‐nmr. All the nonexchangeable protons, as well as the exchangeable imino protons and the phosphorus signals, have been assigned. Both oligonucleotides have been shown to adopt a right‐handed B‐DNA type structure. The addition of ditercalinium to the oligo‐nucleotides lead to the formation of complexes in slow exchange at the nmr time scale with the free helices. At all drug‐to‐helix ratios studied, the ditercalinium was found in the bound form, whereas free and complexed oligonucleotides were in slow exchange, allowing resonance assignments through two‐dimensional chemical exchange experiments.For d(GCGC)2the strong upfield shifts induced on all aromatic protons of both the bases and the drug by complexation with ditercalinium suggest an interaction by intercalation of the two rings. However, the loss of twofold symmetry upon binding, as well as the chemical shift variation of the drug proton signals of one of the chromophores with temperature and concentration, favor a model in which the drug–nucleotide complexes have one ring of the drug intercalated and the other stacked on top of the external base pair. The intermolecular contacts between drug protons and nucleotide protons give a defined geometry for complexation that is consistent with the proposed model.In contrast, with d(CCTATAGG)2several drug–nucleotide complexes were formed and a large increase in line broadening was observed at high drug‐to‐DNA ratios, precluding a detailed analysis of these complexes. However, the large upfield shift in the imino proton resonances together with the shielding of the ditercalinium ring protons favor a model with bis‐intercalation of ditercalinium. This model is supported by the downfield shift of at least 4 out of 14 phosphorus signals. The results are compared with those obtained on ditercalinium binding to the homologous sequences d(CGCG)2and d(TTCGCGAA)2, and discussed i

ISSN:0006-3525    

DOI:10.1002/bip.360310307

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

年代:1991

数据来源: WILEY

ISSN:0006-3525    

DOI:10.1002/bip.360310308

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

年代:1991

数据来源: WILEY

ISSN:0006-3525    

DOI:10.1002/bip.360310301

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

年代:1991

数据来源: WILEY