Principles of modeling in the study of conformations of histones

A study has been made by the CD method of the conformational potentialities of the polypeptides (Gly-Lys-Gly)_n and (Ala-Lys-Ala)_n and fragments of the terminal sections of histones H4 (the sequence 1–16), H2B (1–21), and H1 (152–184), and they have been used as models of histones in complex formation with DNA under various conditions of the medium.V. I. Nikitin Institute of Chemistry, Tadzhik SSR Academy of Sciences, Dushanbe. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 391–398, May–June, 1989.     

Conformational maps of medium-sized rings

A graphical method of quantitative conformational analysis of medium-sized rings that unites earlier concepts is proposed. This method was used to obtain conformational maps of 6–8-membered rings that make it possible to unequivocally determine the conformations of real rings and to show all possible pathways of conformational transitions without depiction of the individual conformations. This approach made it possible to ascertain previously unknown conformations and pathways of conformational transitions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 542–559, April, 1988.     

Conformational features of peptide fragments of the C-end of histone H1

The conformational possibilities of four synthesized oligopeptides with the amino acid sequences 165–172, 173–184, 152–172, and 152–184 of the C-end of histone H1 of calf thymus above been studied in solution under various conditions by the method of circular dichroism.V. I. Nikitin Institute of Chemistry, Academy of Sciences of the Tadchik SSR, Dushanbe. Institute of Cytology, Academy of Sciences of the USSR, Leningrad. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 793–798, November–December, 1990.     

IR spectroscopic study of the conformational lability of 4′-ethyl-4-cyanobiphenyl

The conformational lability of 4-ethyl-4-cyanobiphenyl molecules in solid crystal (SC) and isotropic liquid (IL) states was investigated by IR spectroscopic techniques (experiment and theory). IR absorption spectra were measured at 28°C–95°C in the frequency range 400 cm^–1–4000 cm^–1. Spectrum simulation was performed using the fragment method with allowance for the conformational fluctuations of molecules. The experimental and calculated spectra were compared and analyzed, and it was shown that in the IL, the samples are mixtures of conformers. The temperature changes in the spectra in the stated range are caused by the conformational lability of molecules.Original Russian Text Copyright © 2004 by L. M. Babkov, I. I. Gnatyuk, G. A. Puchkovskaya, and S. V. TrukhachevTranslated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 3, pp. 398–405, May–June, 2004.     

Conformational analysis and electronic structure of acetanilide

The calculations of the electronic structure and conformational analysis of the acetanilide were carried out using the CNDO/2 method. The results show that the endo form is 1.2 Kcal/mole more stable than the exo form. The most stable conformation of the exo isomer corresponds to the dihedral angle of 90 ° between the phenyl and acetamide plane, whereas the minimum energy conformation of the endo isomer corresponds to the dihedral angle 50 °–60 °. A comparison of the calculated and experimental dipole moments suggests also the dihedral angle of 50 °–60 °. A comparison with experiment indicates that this molecular orbital method is good for conformational analysis and gives electronic structure which is compatible with spectroscopic measurement. The calculated conformational analysis and electronic structure of the acetanilide are in excellent agreement with experiments.We thank Professor J. P. Green for helpful discussions. This research was supported by a grant from the National Institute of Mental Health (MH-17489-01).     

Conformational Stability from Variable-Temperature Infrared Spectra of Krypton Solutions, Ab Initio Calculations, and r o Structural Parameters of Chlorocyclopentane

The infrared spectra (3500–400 cm^–1) of krypton solutions of chlorocyclopentane, c-C₅H₉Cl, at variable temperatures (–101 to –150°C) have been recorded and the fundamental vibrations of the axial conformer and several of those for the equatorial form have been assigned. Utilizing two pairs of fundamentals for the two conformers in the krypton solution, an enthalpy difference of 145±15 cm^–1 (1.73±0.18 kJ-mol^–1) has been obtained with the axial conformer the more stable form. It is estimated that there is 67±2% of the axial conformer present at ambient temperature. Convincing spectroscopic evidence shows that a significant percentage of the chlorocyclopentane molecules are undergoing pseudorotation at ambient temperature. The conformational stabilities, harmonic force constants, fundamental frequencies, infrared intensities, and Raman activities have been obtained from MP2/6-31G(d) calculations with full electron correlation and these quantities have been compared to the experimental values when appropriate. The optimized geometries and conformational stabilities have also been obtained from ab initio MP2 calculations as well as by density functional theory (DFT) by the B3LYP method with several different basis sets. The adjusted r ₀ structural parameters have been obtained for both conformers by combining the ab initio data with the previously reported microwave rotational constants. These new values of the structural parameters for both conformers are compared to those previously reported from electron diffraction and microwave studies. These results are compared to the corresponding quantities of some similar molecules.     

Theoretical conformational analysis of tripeptides with a glycine residue

Summary 1. The conformational states of glycine residues — R, B, L, P — in the low-energy forms of the tripeptides (I–III) are found with equal frequency.2. The conformations of the main chain in sections of protein with glycine residues correspond to the preferred forms of the tripeptide fragments (I–III).3. The close-, medium-, and long-range interactions in proteins do not contradict one another and exist at the favorable forms of the main chain.M. M. Shemyakin Institute of Bioorganic Chemistry, Academy of Sciences of the USSR. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 631–637, September–October, 1975.     

Investigation of the effects of hydration and amphiphilic properties of nootropic drugs of piracetam and pramiracetam

An investigation of the hydration and amphiphilic properties of the piracetam and pramiracetam molecules has been conducted by theoretical conformational analysis and the Monte Carlo method; their localization and orientation at the water-lipophilic medium interface have been determined, which made it possible to explain the characteristics of the pharmacological action of the drugs.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 28, No. 4, pp. 355–358, July–August, 1992.     

Influence of solvent on conformational equilibrium in phenyl glycidyl ether

The conformational equilibrium in phenyl glycidyl ether in aprotic solvents was studied by the PMR method over a broad range of changes in the values of the dielectric constant. It was shown that the parameters of the multiplet of noncyclic methylene protons in the PMR spectrum of phenyl glycidyl ether are a sensitive indicator of the position of the conformational equilibrium in the glycidyl fragment. The specific interaction of the molecules of aromatic solvents with the epoxide ring has been discovered.Translated from Teoreticheskaya i Eksperimental'naya Khimiya, Vol. 21, No. 2, pp. 245–247, March–April, 1985.     

A theoretical analysis of the conformation of Ac-L-Ala-L-Pro-L-Ala-NHMe with intramolecular hydrogen bonds

Summary 1. The optimum conformations of Ac-L-Ala-L-Pro-L-Ala-NHMe with eight possible systems of intramolecular hydrogen bonds have been calculated by the method of theoretical conformational analysis.2. The structures found serve as canonical forms for the study of the conformational states of sections of peptide-protein systems with proline residues.3. It has been shown that the interaction of adjacent residues in the structure of the compound mentioned play the dominating role.M. M. Shemyakin Institute of Bioorganic Chemistry, Moscow. Translated from Khimiya Prirodynykh Soedinenii, No. 2, pp. 233–238, March–April, 1976.     

Investigation of complexes of DNA with synthetic peptide fragments of the N-end of histone H2B

The nature of the interaction of high- and low-molecular-weight DNAs (6×10⁶ and 3×10⁵ daltons) with synthetic oligopeptides of the N-end of histone H2B having the sequences 1–21, 1–10, 1–13, 11–21, and 14–21, differing in molecular weight and amino acid composition, as a function of the amount of peptide component in the complex and the ionic strength of the solution has been studied by the methods of UV and CD spectroscopy and the spectrophotometric analysis of melting curves. It has been shown that of all the peptides studied only the 1–21 peptide possesses the capacity of condensing DNA. This capacity depends on the amount of peptide component in the complex, the molecular weight of the DNA, and the ionic strength of the solution. The interaction with peptides under all the conditions studied, without changing the conformational parameters of the DNA, stabilizes its secondary structure in relation to the action of the temperature, which depends on the number of lysine residues in the peptides.N. I. Nikitin Institute of Chemistry of the TadzhSSR Academy of Sciences, Dushanbe. Institute of Cytology of the USSR Academy of Sciences, Leningrad. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 708–713, September–October, 1987.     

Conformational factors in the complexation of tetraoxacrown ethers

The conformational changes in tetraoxacrown ethers (ring size 12–16) during hypothetical reaction with alkali-metal ions were investigated by the method of penalty functions. An analysis is made of the variation of the selectivity curves of crown ethers, calculated by the method of atom—atom potential functions, with variation in the length of the methylene chains between the donor atoms. It is shown that the important factor for the effective complexation of macroheterocycles is not the formal correspondence between the size of the ion and the cavity of the ligand but the possible adjustment of the macrocycle for complementary combination with the cation with minimal expenditures of conformotional energy.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 26, No. 3, pp. 319–324, May–June, 1990.     

Covalent immobilization of heparin on a collagen film

Four procedures for the covalent immobilization of heparin (Hp) on a collagen film (CF) have been investigated. In three of them (methods (I–A, B, C), the CF was first treated with epichlorohydrin and ammonia and the Hp was added with the aid of CMBC (method I–A), by reductive amination in the presence of NaCH CN (method I–B), and with the aid of CMEC after succinylation (method I–C). In the fourth procedure (method II), the CF was activated by treatment with alkali and the Hp was added with the aid of CMEC. It was shown that the maximum amount of Hp was immobilized by method II.M. V. Lomonosov Moscow State University. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 700–704, September–October, 1987.     

New strategy to the synthesis of (N → B) phenyl[N-alkyliminodiacetate-O,O′,N]boranes: The crystal structure of (N → B) phenyl[N-benzyliminodiacetate-O,O′,N]borane, (N → B)phenyl[N-(4-methyl)benzyliminodiacetate-O,O′,N]borane and (N → B) phenyl[N-phenacyliminodiacetate-O,O′,N]borane

A new, mild and friendly method for the synthesis of (N → B) phenyl[N-alkyliminodiacetate-O,O′,N]boranes 2–7 is reported. All compounds were identified by ¹H, ¹¹B, ¹³C NMR and their high resolution mass spectra (HRMS) are reported. The structure of the compounds 2, 4 and 5 were established by single crystal X-ray. Compounds 2 and 4 crystallized with two independent molecules 2A, 2B and 4A, 4B, respectively in the asymmetric unit. These molecular structures established the bicyclic structure showing a N → B bond length of 1.666 (2) Å for 2A, 1.675 (2) Å for 2B, 1.675 (3) Å for 4A, 1.663 (3) Å for 4B and 1.679 (2) Å for 5, as well as different torsion angles of the junction, 28.70 (2)° (C11–B1–N6–C17) for 2A, 21.50 (2)° (C11a–B1a–N6a–C17a) for 2B, 25.76 (0.26)° (C11–B1–N6–C17) for 4A, 21.96 (0.28)° (C11a–B1a–N6a–C17a) for 4B and −29.22 (0.20)° (C5–N1–B1–C13) for 5.     

Determination of ginkgolide A,B, and bilobalide in<Emphasis Type="Italic"> biloba</Emphasis> L. extracts by microdialysis-HPLC

A method has been developed for measuring ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts by using a self-assembled microdialysis device coupled on-line to high-performance liquid chromatography. The optimal conditions for dialysis efficiency and chromatographic analysis were investigated. The results show that the dialysis efficiencies for ginkgolide A, B, and bilobalide are 97.8–100.4%. For the spike concentration of 45 mg L^–1, the recoveries of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts were at 97–100.7% with 3.1–4.7% RSD. The proposed method has therefore been shown to be applicable to the analysis of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts.     

Conformational dependence of the intrinsic acidity of the aspartic acid residue sidechain in N-acetyl- -aspartic acid-N′-methylamide

The sidechain conformational potential energy hypersurfaces (PEHS) for the γ_L, β_L, α_L, and α_D backbone conformations of N-acetyl- -aspartate-N′-methylamide were generated. Of the 81 possible conformers initially expected for the aspartate residue, only seven were found after geometric optimizations at the B3LYP/6-31G(d) level of theory. No stable conformers could be located in the δ_L, _L, γ_D, δ_D, and _D backbone conformations. The ‘adiabatic’ deprotonation energies for the endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide were calculated by comparing their optimized relative energies against those found for the seven stable conformers of N-acetyl- -aspartate-N′-methylamide. Sidechain conformational PEHSs were also generated for the estimation of ‘vertical’ deprotonation energies for both endo and exo forms of N-acetyl- -aspartic acid-N′-methylamide. All backbone–sidechain (N–H⁻O–C) and backbone–backbone (N–HO=C) hydrogen bond interactions were analyzed. A total of two backbone–backbone and four backbone–sidechain interactions were found for N-acetyl- -aspartate-N′-methylamide. The deprotonated sidechain of N-acetyl- -aspartate-N′-methylamide may allow the aspartyl residue to form strong hydrogen bond interactions (since it is negatively charged) which may be significant in such processes as protein–ligand recognition and ligand binding. As a primary example, the molecular geometry of the aspartyl residue may be important in peptide folding, such as that in the RGD tripeptide.     

Molecular structure and properties of benzo-12-crown-4 and acetylbenzo-12-crown-4

Conclusion Significant differences were found in the conformational states of B12C4 and acB12C4 in solution, which are capable of affecting the complexation properties and physiological activity of these polydentate ligands.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1051–1055, May, 1988.     

Thermally induced early events of ribonuclease A under reducing conditions: Evidenced by principal component analysis and two-dimensional correlation infrared spectroscopy

The thermally induced unfolding of ribonuclease A in the presence of 2-mercaptoethanol has been followed by fluorescence spectroscopy and Fourier transform infrared (FTIR) spectroscopy. Principal component analysis (PCA) in combination with two-dimensional (2D) infrared correlation spectroscopy has been employed as an attractive method for the investigation of subtle pretransitional conformational changes in the protein. Separate analyses of different stages indicated that, in stage I the change of β1(43–49) and α2(24–34) might be the main process; in stage II, β1 was further unfolded, changes of α1(3–13) and another species of β2(61–63) and β4(79–87) involved. Furthermore, quantitative analysis of the power spectra extracted from the synchronous 2D contour maps revealed that the intensity variations from pretransitional stages (below 47 °C) were 5% less than that for the main unfolding. Meanwhile, under reducing conditions the early subtle structural changes occurred in a non-cooperative manner, in contrast to what was found under non-reducing conditions.     

A proposed bioactive conformation of Peptide T

The conformational profiles of Peptide T, (5–8)Peptide T, [Abu⁵](4–8)Peptide T and (4–8)Peptide T were computed independently to assess the geometrical characteristics of the bioactive conformation of Peptide T. The conformational profiles of the peptides were computed within the molecular mechanics framework using an effective dielectric constant of 80. The conformational space was thoroughly sampled using an iterative simulated annealing protocol. The bioactive conformation was assessed by pairwise cross comparisons of each of the unique low energy conformations found for each of the different analogs studied. After a putative bioactive conformation was selected, in order to further validate our hypothesis the conformational profile of the potent compound cyclo(Thr-Thr-Asn-Tyr-Thr-Asp) was computed and the putative bioactive conformation was found. The conformation exhibits a pseudo -turn involving the side chain of Thr⁵ and the carbonyl oxygen of Tyr⁷ forming a C12 ring.