Theoretical studies on the conformation of monosialogangliosides and disialogangliosides

The preferred conformation of gangliosides GM3, GM2, GM1, GD1a and GD1b have been studied by computing their potential energies. The conformation of NeuNAc in GM3 differs from that expected for the same residue in GM2 and GM1. The NeuNAc residues in GM2 and GM1 exhibit identical conformations. Theory predicts that the terminal NeuNAc of GD1a is conformationally similar to that of GM3 and that the internal one is similar in conformation to those present in GM2 and GM1 in agreement with NMR studies. The differences in chemical shifts of the C2 and C3 carbons of the internal and terminal NeuNAc of GD1a have been attributed to differences in orientation. The present studies suggest that the binding site of cholera toxin is much smaller than that of tetanus toxin. The preferred shape of these gangliosides correlate well with their biological properties.     

Theoretical studies of protein conformation by means of energy computations

In this review we describe fundamental concepts and applications of conformational energy computations, with emphasis on some recent advances and problems being investigated. The formulation of potential energy functions is described, including the nature of the intramolecular force field, the representation of interactions with the solvent, and considerations of entropy contributions. Approaches to the search for the optimal potential energy are summarized. Examples cited among applications of conformational energy computations include refinement of X-ray crystallographic structures, the use of computations in conjunction with NMR data, prediction of the structures of proteins based on either homology or on other procedures that surmount the multiple-minima problem, the analysis of hierarchical levels of structure and assembly, and interactions in enzyme-substrate complexes.     

Theoretical studies on the conformation of saccharides. XIV. Structure and conformational properties of the glycosylamines

The 2-methylaminotetrahydropyran was used as a model to study conformational properties of the N-glycosidic linkage in glycosylamines. Relaxed two-dimensional conformational (phi, psi) maps in 20 solvents were calculated by a method in which the total energy is divided into the energy of the isolated molecule and the solvation energy. Molecular geometry optimization has been carried out for each conformer using the quantum chemical method PCILO. The calculated variations of the geometry are consistent with the results obtained by the statistical analysis of available experimental data retrieved from the Cambridge Structural Database. The calculated abundances of conformers show that the polarity of the solvent has little effect on the anomeric ratio, and the form having the methylamino group equatorial is favored in all considered solvents.     

Spectral studies on the conformation of rhodopsin

A summary is given of visible and ultraviolet spectral studies which deal with the conformation of rhodopsin in situ and solubilized with detergent. Emphasis is placed on studies which give specific information about the macromolecular structure and which set quantitative limits on the magnitude of light-induced conformational changes.Presented at the EMBO-Workshop on Transduction Mechanism of Photoreceptors, Jülich, Germany, October 4–8, 1976     

Theoretical conformation analysis of MCD peptide

The spatial structure of the MCD-peptide from bee venom has been calculated basing on the known sequence of 22 amino acid. The a priori calculations produce a system of two disulfide bonds, identical to that observed in the native structure. The calculated structure of MCD-peptide is close to that proposed earlier for the homologues peptide tertiapin and is confirmed by NMR and CD data.     

Rapid kinetic studies on the conformation of single-stranded DNA

The conformational states of single-stranded calf thymus DNA were probed using the tmeperature-jump kinetic technique. A rapid decrease in transmission at 260 nm followed by a broad relaxation spectrum was observed for single-stranded DNA at 0.15M KCI, pH, 6.5 at 25°. The relaxation spectrum could also be detected as a hydrogen ion release. Sonicated samples of 103,000 daltons showed identical relaxation kinetics as unsonicated samples. The relaxation kinetics were studied as a function of temperature, pH, and salt concentration and could be interpreted as representing the melting of short, isolated folded segments. The rapid process that could not be kinetically resolved is interpreted as single-strand unstacking. Upon the addition of excess MgCl₂ at pH 7.0, a hydrogen ion release from single-stranded DNA was observed that was 3.5 times greater than that observed for a comparable sample of native DNA. Evidence is presented which indicates that charge-pairs exist in folded segments that are A-T rich. There was no kinetic evidence of structures in single-stranded DNA other than single-stranded stacking and short isolated folded regions.     

Conformational studies of proteoglycans: theoretical studies on the conformation of heparin.

Various models proposed for heparin have been examined by a stereochemical approach involving contact distance criteria and potential energy calculations. The present study suggests that the model favored by Atkins and coworkers [Biochem. J. (1973) 135 , 729–733 and (1974) 143 , 251–252] is not stereochemically satisfactory. An alternative model has been proposed with N-acetyl-D -glucosamine and one of the uronides in the ⁴C₁ conformation and the other uronide (probably sulfated) in the ¹C₄ conformation. The observed variations in the tetrasaccharide periodicities (16.5–17.3 Å) in different crystalline modifications of heparin have been attributed to possible changes in the rotational angles about the interunit glycosidic bonds rather than a change in the pyranose ring conformation. The proposed model is also independent of the observed variation in the relative composition of uronic acid residues in heparin. These conclusions are in disagreement with those of earlier workers.     

Theoretical studies on the conformation of saccharides. VIII. Solvent effect on the stability of β-cellobiose conformers

The conformational equilibria of five β-cellobiose conformers have been studied theoretically in 10 solvents. The stability of the conformers in dilute solution has been compared by using the method that has already been tested for 2-methoxytetrahydropyran, β-maltose, and D -glucose. The solvation energy consists of electrostatic, dispersion, and cavity terms which have been determined from the properties of the solute calculated by the PCILO quantum-chemical method and physicochemical properties of the solvents. The calculated abundance of conformers depends on the solvent (e.g., in dioxane C1:C2:C3:C4:C5 = 60.0:34.1:2.9:2.0:1.0; in dimethylsulfoxide, 75.5:22.1:1.8:0.5:0.2; and in water, 82.2:16.2:1.3:0.2:0.1). The results obtained indicate that the preponderant conformer in the aqueous solution is similar to the one adopted by β-cellobiose in the crystalline form. The role of individual contributions to the solvation energy have been analyzed. Based on the determined abundance of conformers, averaged residual optical activity and nmr parameters have been calculated and compared with observable properties. The marked differences observed between solvent-induced conformational changes for β-cellobiose and β-maltose have been discussed from the viewpoint of the solubility of the cellulose.     

Theoretical studies on the conformation of saccharides. IV. Solvent effect on the stability of β-maltose conformers

The conformational equilibria of four β-maltose conformers have been studied theoretically in 12 solvents. The stability of the conformers in dilute solution has been compared by using the continuum reaction field method. The solvation energy consists of electrostatic, dispersion, and cavity terms, which have been determined from the calculated properties of β-maltose and physicochemical properties of solvents. The calculated population of four conformers significantly depends on the solvent (e.g., in dioxane, M1:M2:M3:M4 = 53.3: 20.3:17.7:8.7; in dimethyl sulfoxide, 40.1:21.8:22.8:15.3; and in water, 25.7:17.5:26.3:30.5) and was found to correlate with experimentally observed data. The results obtained indicate that the conformation adopted by β-maltose in the crystalline form is not the one preferred in solution. The roles of the individual contributions to the solvation energy have been analyzed. Based on the determined abundance of conformers, averaged residual optical activity and vicinal carbon–proton coupling constants have been calculated and discussed from the point of view of the solution behavior of β-maltose.     

Theoretical conformation analysis of beta-casomorphin-5 molecule

The spatial structure of beta-casomorphin-5 molecule--H-Tyr-Pro-Phe-Pro-Gly-OH has been investigated by the theoretical conformational analysis method. The results indicate that the conformational properties of the molecule can be represented by a large number of structures having twelve different backbone forms.     

Theoretical study of prostaglandin E2 conformation

The theoretical conformational analysis of PGE2 has been performed using semiempirical approach and fixed values of the bond length and valence angles. A set of low-energy conformations was obtained for the alpha-chain and the whole PGE2 molecule. Unlike the PGE1 molecule, PGE2 alpha-chain prefers semifolded conformations. The hairpin structures with the parallel orientation of alpha- and omega-chains are the lowest-energy conformations of PGE2 conformations of PGE1 and PGE2. Sterically similar explain the similar biological activity of the two molecules.     

Methods of peptide conformation studies

In solution most of the peptides assume multiple flexible conformations. Determination of the dominant conformers and evaluation of their populations is the aim of peptide conformation studies, in which theoretical and experimental methods play complementary roles. Molecular dynamics or Monte Carlo methods are quite effective in searching the conformational space accessible to a peptide but they are not able to estimate, precisely enough, the populations of various conformations. Therefore, they must be supplemented by experimental data. In this paper, a short review of the experimental methods, most widely used in peptide conformational studies, is presented. Among them NMR plays the leading role. Valuable information is also obtained from hydrogen exchange, fluorescence resonance energy transfer, and circular dichroism measurements. The advantages and shortcomings of these methods are discussed.     

Molecular dynamics studies of the conformation of sorbitol

Molecular dynamics simulations of a 3 molal aqueous solution of d-sorbitol (also called d-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data support a more bent structure.