Chiroptical properties of S-proline conformational isomers

The chiroptical properties of S-proline conformational isomers are examined on a theoretical model in which electronic wave functions are obtained from semiempirical molecular orbital calculations. The CNDO/S molecular orbital model is used to perform SCF-MO calculations on ground state electronic structure and excited states are constructed in the virtual orbital-configuration interaction approximation. Electronic rotatory strengths and dipole strengths are calculated directly from the complete (but approximate) molecular electronic wave functions. Zwitterionic, cationic, and anionic S-proline structures are studied twotypes of conformational variables are represented in the calculations: (1) pyrrolidine ring conformation; and (2) rotation about the C^α-COO^? bond. Rotatory strengths are found to be somewhat sensitive to rotational isomerism about the C^α-COO^? bond, but are found to be rather insensitive to conformational changes within the pyrrolidine ring. The CD spectrum of zwitterionic S-proline down to ～160 nm appears to be well accounted for by the theoretically calculated results if conformational preferences with respect to rotation about the C^α-COO^? bond can be assumed to exist in solution media. Furthermore, spectra-structure correlations are offered for the anionic and cationic forms of S-proline in solution.     

Theoretical conformational analysis of oxytocin molecule.

The total semi-empirical conformational analysis of the oxytocin molecule has been carried out. It has been revealed the two main types of stable structures of cyclic moiety backbone and the great lability of the tail. The optimal spacing of cyclic moiety side chains has been found for every backbone structure. The calculation results are in good agreement with the data of physico-chemical investigations. Among the set of stable molecule structures reported in the present study are structures with beta-turn conformation of the cyclic moiety backbone and without closer spacing of the cyclic moiety and the tail, as well as structures with closely spaced N- and C-terminal parts which, however, lack beta-turn in the cyclic moiety.     

Beta-carbonylamides in peptide chemistry. I. Optical rotatory properties of N-acetoacetyl amino acids

The Cotton effects of N-acetoacetyl amino acids and derivatives were examined by a circular dichroism technique. A correlation has been established between the sign of the Cotton effect and the absolute configuration of the asymmetric center. The L derivatives show, in dioxane, negative circular dichroism curves, whereas the D antipodes present positive curves. The effect of solvent and pH and influence of alkylation at the amide nitrogen are also discussed.     

Theoretical conformational analysis of tripeptides. N-acetyl-L-alanyl-L-alanyl-L-alanyl methylamide]

The minimization procedure has been used for calculation of the local minimum conformations of threepeptide--Ac-(L-Ala)3-NHMe without intramolecular H-bonds. The significant energy deviations from additivity found, arising with increase backbone length to three links, can be considered as the evidence for mutual dependence of conformational states of the neighbouring and terminal amino acid residues. It have been shown that stability of alpha-helix form for alanine threepeptide in contrary to corresponding dipeptide is noticeably higher due to stabilizing effect of dispersion interactions. The results of calculations are compared with the data on conformational distrubution of the threepeptide fragments in proteins with known three dimensional structure. The important role of the backbone interaction in protein chain have been marked.     

Theoretical conformational analysis of brain peptides. beta-Melanocyte-stimulating hormone

Using a semi-empirical method, an a priori conformational analysis of the octadecapeptide beta-melanocyte-stimulating hormone (beta-MSH) was carried out. The spatial structure of beta-MSH can be described by eight low-energy conformations, yielded by combinations of the most stable states of the respective free fragments. Calculations produced the values of all dihedral angles of the backbones and side chains of these forms as well as intra- and inter-residue interaction energies.     

Theoretical conformational analysis of phospholipids bilayers

We present a computational approach describing the conformation of lipid molecules (1-2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC)) organized in bilayers. The classical semi-empirical method used in peptide conformational analysis has been extended successfully to lipids. The excellent agreement between our theoretical predictions and recent experimental data on the molecular organization of lipid bilayers suggests that the method could be a valuable tool in the lipid conformational analysis but also in the prediction of orientation and mode of insertion of amphiphilic molecules into the lipid bilayer.     

Theoretical conformational analysis of a family of alpha-helical immunocytokines.

According to the results of the theoretical conformation analysis and available experimental data, the known immunocytokines can be divided into two groups: alpha-helical (IFNs-alpha, beta, gamma, omega; IL-2, 3, 4, 5, 6, 7; G-, M-, GM-CSFs; cMGF, PDGF) and beta-pleated proteins (ILs-1 alpha, beta; TNFS-alpha, beta). IFNs-alpha, beta, gamma, omega, IL-6, G-CSF, cMGF were shown to form a family of alpha-helical globular proteins characterized by a statistically significant homology in amino acid sequences and by common features of the secondary structure formation. Comparison of the sequences of 72 IFNs-alpha, beta, omega reveals three clusters of conservative amino acid positions. Their participation in the formation of active sites of IFN-alpha, beta, omega is supposed.     

Theoretical conformational analysis of methylamide N-acetyl-L-arginine]

The spatial structure of methylamide N-acetyl-L-argine was studied taking into account the non-valent and electrostati interactions, the torsion energy, and the distorsion of valency angles. Calculation of the favourable conformations of the molecule was carried out with the use of all the combinations of angles phi, psi, chi1 divided by chi4 as an intital approximation. These correspond to the low energy forms of the main chain and to the minima of the torsion potentials of the side chain. Conformational possibilities of arginine and lysine were compared. The calculated stable conformation of N-acetyl-L-arginine-methylamide are compared with the geometry of arginine residues in the proteins with known structure.     

Theoretical conformational analysis of doulble-stranded polynucleotides]

Calculations of intramolecular interaction energy of two-stranded helical homopolynucleotide in the function of nine conformational variables have been carried out by the method of atom-atom potential functions. Four of these variables determine mutual position of base pairs, other four--deoxiribose ring conformation and other one--orientation of this ring with respect to the base. For this purpose an algorythm connecting dependent variables with independent ones has been developed. The investigation of energy function has shown that in the space of conformational parameters there are two valleys, which correspond to A-and B-families of conformations. Experimentaly determined conformations of two-stranded helical polynucleotides are located along the bottoms of these valleys. Along the bottom of each valley the intramolecular interaction energy changes rather little when conformational parameters change within a wide range. The valleys are separated by an energetical barrier.     

Oligonucleotide studies. Optical rotatory dispersion of five homodinucleotides

1. The optical rotatory dispersion (ORD) of five homodinucleotides, ApAp(3'), CpCp(3'), GpGp(3'), IpIp(3') and UpUp(3') (where A, C, G, I and U represent adenosine, cytidine, guanosine, inosine and uridine respectively, and p to the left of a nucleoside symbol indicates a 5'-phosphate and to the right it indicates a 3'-phosphate), were measured as a function of pH, ionic strength and Mg(2+) concentration. 2. The ORD titrations of ApAp(3') and CpCp(3'), which were made by measuring the ORD curves at closely spaced pH intervals, exhibit a maximum at approx. pH5.0 and 5.7 for ApAp(3') and CpCp(3') respectively in the profile of the magnitude of the first Cotton effect versus pH. The results indicate that the conformational rigidity of these dinucleotides depends on the ionization state of a 3'-terminal phosphate group. 3. ApAp(3') was shown to exist as an approximately 1:1 equilibrium mixture of the two major ionic species represented by Ap((-1))Ap((-1)) and Ap((-1))Ap((-2)) at pH6.16, whereas at pH7.5 it exists exclusively as a form of Ap((-1))Ap((-2)). 4. To ascertain the effects of the presence of a terminal phosphate group and of the ionization of the secondary phosphate on the conformation of adenylate dimer, we measured the ORD of ApA, ApAp(3')CH(3) and ApAp(2'). The rotatory power of the first Cotton effect in the above series of dinucleotides decreased at 20 degrees in the order ApA> ApAp(3')CH(3) approximately ApAp(3')((-1))> ApAp(2') at pH7> ApAp(3') at pH7. 5. The pH-rotation profiles were also obtained for ApAp(2'), CpCp(2') and UpUp(3'), but no corresponding maximum was observed. Although simple nearest-neighbour calculations based on the ORD data of IpIp(3') and 5'-IMP account for the observed ORD spectrum of polyinosinic acid at low salt concentration, there were large discrepancies between calculated and experimental results of the polyguanylic acid ORD even at low ionic strength. 6. The extent to which the amplitude of the Cotton effects of IpIp(3') increases with salt concentration, especially by the addition of Mg(2+), was much greater than that observed for ApAp(3'). The implication of such salt effects on the ORD is considered.     

Theoretical conformational analysis of methylamide of N-acetyl-L-lysine]

The spatial structure of the methylamide of N-acetyl-L-lysine has been analysed taking into account non-bonded and electrostatic interactions, torsional energy, bond angles distortion and hydrogen bonding. Conformational capacities of the backbone and mutual dependence of spatial structures of the backbone and the side chain was described by conformational maps obtained by energy minimisation, the dihedral angles and the bond angles of the side chain being varied for every phi, psi point. Every possible combination for phi, psi, x1-x5-angles was used corresponding to the stable form of the backbone and to torsion potential minima of the initial approximations in the calculation of preferred conformations of the molecule. Comparisons are made between stable forms of the methylamide of N-acetyl-L-lysine and Lys residues in proteins with known structure.