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 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.     

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 study of the hypochromic effect in polynucleotides]

The first UV-absorption band hypochromicity of poly(dA)-poly(dT), poly(dG)-poly(dC), poly(dA), poly(dT), poly(dG), poly(dC), is calculated with the help of the perturbation theory. The wave functions of the bases are computed by Pariser--Parr--Pople's method taking into account all the singly excited configurations. The results obtained show a good correlation between the theoretical and experimental values of hypochromicity. A considerable influence of the vaccum electron transitions on the hypochromicity of polynucleotides is revealed. The origin of the hypochromic effect in the double-stranded polynucleotides is investigated. It is shown that intrastrand interactions between the bases make the main contribution to hypochromicity (60-76%), while the contribution of the Watson-Crick pairs is small (2-12%). The essential part of hypochromicity (22-28%) is due to the interstrand interactions between the bases which are not coupled by hydrogen bonds. The discussion of the experimental data shows that the present theoretical investigation could serve as a basis for correct treatment of experimental results.     

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 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.     

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.     

The influence of complementary base pair interactions on secondary structure formation and conformational transitions in polynucleotides]

The calculations have been carried out of interaction energy between complementary base pairs of nucleic acids in the function of conformational parametres of double helix (Arnott's parameters) by the method of atom-atom potential functions. Interaction energy as a function of conformational parametres is valley-like and varies little along the bottom of the valley. The regions of interaction energy minima are compared with experimentally determined conformational parametres of nucleic acid double helices. On the basis of calculation results the pathways of conformational transitions between different forms of double-helical polynucleotides are discussed.     

Theoretical conformational analysis on Cyclo(prolyl-phenylalanyl) peptides

Empirical energy calculations on cyclo(L -Pro-L -Phe) and cyclo(L -Pro-D-Phe) indicate that different conformations are possible for each molecule. The theoretical results are compared to ir, nmr, and crystallographic data. The interdependence between diketopiperazine ring and side-chain conformations is also discussed.     

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 analysis of competitive conformational transitions in torsionally stressed DNA

This paper presents a theoretical analysis of the conformation of a torsionally deformed segment of DNA containing two sites susceptible to stress-induced transitions in secondary structure. A mechanical analysis of the ensuing competitive behavior is developed and applied to several phenomena of possible biological relevance. First, a molecular lesion which disrupts base pairing without strand breakage (such as a pyrimidine dimer) is shown to provide an effective nucleation site for further stress-induced denaturation. A competition is established between strand separation at this lesion site and at the A + T-richest portion of the molecule. The relative importance of these two forms of melting is shown to depend upon the A + T-content of the sites involved, segment length, local environmental conditions and the magnitude of the imposed torsional deformation. A possible alternative mode of behavior of a stressed segment of DNA involves transitions from B-form to Z-form. The second application of this theory analyzes the interplay between B → Z transitions and local denaturation in torsionally stressed DNA. Finally, local melting is shown to be energetically preferred over transitions to A-form under physiologically reasonable conditions in vitro, due primarily to the greater degree of unwinding involved in melting.The mechanical theory presented here makes several simplifying assumptions regarding the nature of the transitions and the sequences involved. First, the theory is developed explicitly for the competition between two sites of possible transition, with no further consideration given to conformational degeneracy or sequence effects. These sites are regarded as being uniform in composition. A multistate, heteropolymeric statistical mechanical transition theory is required to account rigorously for degeneracy and the influence of base sequence. A preliminary formulation of such a theory is used to analyze the denaturation of a segment containing a site of disrupted base pairing.     

Optical rotatory properties of L-cystine conformational isomers. Theoretical analysis

The near ultraviolet chiroptical properties of L -cystine conformational isomers are examined on a static, “one-electron” model in which the disulfide moiety is the chromophoric group and the atoms of the L -alanyl fragments are treated as perturbers. The zeroth order chromophoric wave functions are calculated on a semiempirical molecular orbital model in which excited states are constructed in the virtual orbital-configuration interaction approximation. The perturbing environment is represented by point charges located at the atomic centers of the L -alanyl fragments. Chromophore–perturber interactions are expressed as charge–multipole moments with only the charge–dipole and charged–quadrupole terms being retained in the calculations. Vicinal contributions to the rotatory strengths of the five lowest energy disulfide transitions are computed for 30 conformational isomers of the L -cystine dizwitterion. The results provide support for the view that vicinal or peripheral effects can account entirely for the observed near ultraviolet (λ > 230 nm) chiroptical properties of L -cystine and its derivatives and that these properties are diagnostic of conformational features external to the disulfide moiety.     

A soft-modeling approach to interpret thermodynamic and conformational transitions of polynucleotides

Multivariate outputs from the experimental monitoring of biochemical processes are usually difficult to interpret applying methods based on a priori chemical models. Curve resolution methods are model-free procedures, generally known as soft-modeling methods, which obtain the concentration profiles and instrumental responses of each individual species involved in a multivariate monitored process without making any kind of external assumption. Of the curve resolution methods available, the alternating least squares (ALS) is proposed here because of its ability to operate on one or on several matrices. Furthermore, ALS allows the introduction of information related to the internal data structure and to the general features of the concentration profiles and instrumental responses through the input of suitable constraints in the iterative resolution procedure. The ALS potential is tested on several data sets coming from the multivariate spectrometric monitoring of polyuridylic (polyU), polycytidylic (polyC), and polyadenylic (polyA) protonation equilibria in dioxane/water 30% (v/v). Information concerning the evolution of the concentration profiles and the spectra of each individual species involved in the acid-base equilibria, the presence and pattern of polyelectrolyte effects, and the presence of conformational transitions associated or not with the proton uptake process is presented.     

Internal rotation potentials in polynucleotides]

An empirical potential function for internal rotation around P-O bonds in polynucleotides is suggested. Its parameters have been determined taking into account the result of quantum mechanical calculations for dimethylphosphate.