Classical Potential Functions Research Articles

Molecular orbital computations of the conformational energy of ethyl methyl phosphate

As part of a research aimed at an improvement of the description of conformations of polynucleotide chains, we carried outab initio SCF-MO computations on 24 conformations of ethyl methyl phosphate (EMP), a molecule which can be taken as a model for the ω′-rotation of polynucleotides. Quantum-mechanical energies were then reproduced, with good accuracy (standard deviation of fitted fromab initio values 0.12 kcal mole−1), through a classical potential function consisting of a “6–12” Lennard-Jones plus a Coulomb term, and a contribution with twofold periodicity accounting for the anomeric effects in the phosphate group.

Conformational energy analysis of substituted diphenylethanes: Part VI. Calculations of the solvent dependence of the conformational equilibria in stilbene dihalogenides. Intramolecular interactions in the PCILO fr

As part of a theoretical analysis of the conformational equilibria of stilbene dihalogenides, the free energy at 300 K of each stable conformational isomer of these molecules has been estimated for a solvent of dielectric constant 3.5. Classical empirical potential functions were used. Interaction with the solvent was considered only in terms of a continuous dielectric medium interacting with the local dipoles and quadrupoles of the molecule. Simulation of the experimental conditions (i.e. appropriate values for the dielectric constant of the solvent) yielded better agreement with the available experimental data, which were mainly dipole moments and optical rotation values. The quadrupole energy term has a very small influence on the calculated conformational populations and can be neglected when dibenzyl derivatives are considered. The mechanism of the intramolecular interactions is discussed within the PCILO framework.

Organization of phospholipids in biological membranes

AbstractPreferred conformations of phospholipids have been predicted through quantum‐chemical techniques and classical potential functions. An essential condition for a conformation to exist in a biomembrane is that it should be possible for it to organize in the form of a bilayer. Taking into consideration the conformational flexibility of the polar head group, organization at the lipid–water interface has been considered. The biological implications of such an organization in terms of formation of “hydrophobic channels” is discussed. Quantum‐mechanical investigations on the transport phenomenon have shown that the “selectivity” of biological membranes is connected with the “organization.” Calculations of the quantum‐mechanical transmission coefficients for different model potential profiles indicate that minor differences in the height of potential barriers in certain regions can lead to significant changes in transmission coefficients. The “directional selectivity” of substrates (differences in transmission coefficients for flow in and out of the cell) can be explained on the basis of differences in membrane organization. These results have some important consequences in the evolutionary process in biological membranes.

Conformational structure of glycerol trivalerate and its relation to phospholipids: Studies by NMR and potential energy calculations

The structure of a model lipid (glycerol trivalerate, GTV) has been investigated by 1H and 13C NMR, and energy calculations based on classical potential functions (CPF). The structure of glycerol-ester pivot in GTV is characterized by a dynamic equilibrium between two dominant conformations. One of the two conformations (SA) is similar to the reported crystal structure of triglycerides β-triaurin and β-tricaprin and has the following conformational angles: θ 1 = 52°, θ 3 = 46°, α 1 = 208°, β 1 = 156° and γ 1 = 186° . The other conformer (SB) is similar to the reported crystal structure of β and γ chains in 1,2- dilauroyl-D,L- phosphatidylethanolamine and has the conformational angles: θ 1 = 287°, θ 3 = 155°, α 1 = 195°, β 1 = 85° and γ 1 = 194° . The ester groups acquire a rigid planar conformation ( α 2, β 2, γ 2 = 180° ), while the potential energy curves for rotation around the chemical bonds OCOCCC( α 3, β 3 and γ 3 ) indicate a high degree of flexibility. The hydrocarbon chains show a distribution of the gauche and trans conformations around CCCC bonds with a preference for the trans arrangement by almost 0.8 kcal/mol. The conformational picture of the hydrocarbon chains and glycerol moiety in GTV is very similar to that in phospholipids. These results indicate caution in using the reported crystal structure of 1,2- dilauroyl-D,L- phosphatidylethanolamine as the only model for the organization of lipid molecules in biological membranes.

Structure of poly 8-bromoadenylic acid; conformational studies by CPF energy calculations.

Poly 8-bromoadenylic acid [poly(BBrA)] is the only known all-syn polynucleotide. It shows a helix-coil transition with a melting curve centred around 55 degrees C. Energy calculations based on classical potential functions have been used to explore the three-dimensional structure of this polymer in helix and random coil. It is concluded that the ordered state is a helix of two parallel strands with a two-fold rotation axis, and the duplex is stabilised by hydrogen bonds involving N1 and H6. Each strand has a conformation with C3' endo geometry, phi' = 216 degrees, omega' = 280 degrees, omega = 294 degrees, phi = 179 degrees, chi = 243 degrees and psi = 57 degrees. Such a conformation leads to approximately 8 nucleotide units per turn of the helix and an axial rise of 3.9A degrees. The structure of poly(8BrA) has been compared with that of the related polymer poly(A) which forms a double helical structure in acidic conditions with bases in the anti conformation and with interstrand hydrogen-bonds between N7 and H6. This is the first time that a specific geometrical model of a novel polynucleotide structure has been produced initially by potential energy calculations, though such calculations on a number of known structures have been reported previously.

Conformation of N-formyl-1,3-dihydroxy-Δ 31-pentene, a model compound of sphingomyelin

The conformations of 2S,3R-2-( N-formyl)amino-l,3-dihydroxy- Δ 31-pentene, a model compound of sphingomyelin, have been studied both by the classical potential function and by the INDO molecular orbital method. The results suggest that the preferred conformation of sphingomyelin in the membrane is such that the olefinic double bond of the γ-hydrocarbon chain and the planar amide group of the β-chain are parallel and stack in an antiparallel manner with dihedral angles β 1′(C3-C2-N21-C21) = −100 ° and γ 1(C2-C3-C31-C32) = −100 °.

Theoretical studies on pro-leu-gly-nh2 conformation.

Classical potential function calculations were carried out on the hypothalamic factor Pro-Leu-Gly-NH2. The results indicate that the proposed 10-membered, hydrogen-bonded beta-turn conformation of this tripeptide is a strongly preferred structure. Its stability appears to be inherent in the rather rigid backbone conformation of the leucine residue rather than the hydrogen bond between the carboxamide proton of glycinamide and the C=O of the proline moiety; the glycinamide has little influence on the phi-psi of the leucine backbone structure. The type II beta-turn structure of the Pro-Leu-Gly-NH2 is preferred.

Elasticity Solutions for Thick-Wall Submersible Spheres

Elasticity solutions utilizing the classical Boussinesq potential functions for thick-wall submersible spheres are developed. The solutions provide field stresses and strains, which consider the effect of gravity body forces, and arbitrary boundary loadings. The boundary loadings may be due to a nonuniform hydrostatic pressure, hull equipment, ballast, and can be expressed as an infinite series of Legendre polynomials. A numerical example which considers a nonuniform hydrostatic pressure and an arbitrary counter-buoyancy force applied at the inner boundary is given. Field stresses and strains are presented for various shell thicknesses and hydrostatic pressures.

Spatial configuration of single-stranded polynucleotides. Calculations of average dimensions and Nmr coupling constants.

AbstractThe probability distributions of the torsional angles (Φ′, ω′, ω, Φ, and ψ), which fix the structure of nucleotide backbone, have been calculated using the results of energy calculations based on extended Huckel theory (EHT), complete neglect of differential overlap (CNDO), perturbative configuration interaction using localized orbitals (PCILO), and classical potential functions (CPF) methods. Statistical average values of the vicinal 1H1H, 1H31P, and 13C31P nmr coupling constants 〈J〉 have been calculated from the generalized Karplus relations using the probability distribution in the Φ′, Φ, and ψ space. Experimental 〈J〉 values for polyribouridylic acid (polyU) support the theoretical predictions for these torsional angles. Using Monte Carlo technique, random coils of single‐stranded polynucleotides have been simulated and the mean‐square end‐to‐end distance 〈r2〉 has been calculated. Molecular orbital methods (EHT, CNDO, and PCILO) suggest considerable flexibility around OP bonds, leading to fairly small values for the characteristic ratio (C∞ ∼ 4). Observed values of the unperturbed characteristic ratio for polynucleotides are quite large (C∞ ∼ 18) suggesting a relatively rigid nucleotide backbone. The results based on molecular orbital calculations can be reconciled with the experimental values by introducing an additional stabilization of ∼2 kcal mol−1 for the predicted minimum energy ragion (Φ′ ∼ 240°, ω′ ∼ 290°, ω 290°, Φ 180°, and ψ 60°). Such a stabilization may arise from the association of water molecules and metal ions with the phosphate group and (or) Coulomb interaction between neighboring phosphate groups. The calculations provide a semiquantitative estimate of torsional rigidity in the nucleotide backbone.

Quantum chemical studies on the conformational structure of nucleic acids IV. calculation of backbone structure by CNDO method

Quantum chemical calculations using the CNDO/2 method, have been carried out to determine the energetically favoured ranges of the torsional angles (φ′, ω′, ω, φ, ψ) which fix the conformational structure of nucleic acid backbone. The two dimensional isoenergy maps have been constructed in the (ω′, ω) and (φ, ψ) hyperspaces. The variation of total energy with respect to φ′ has also been studied. The results show that the non-bonding interactions play a major role in the conformational stability of nucleic acids and polynucleotides. The theoretical predictions show good correspondence with the experimental data (X-ray and 13C NMR) as well as the other reported theoretical calculations (EHT, PCILO and classical potential functions). The most favoured structure has the conformational angles close to 240, 290, 290, 180 and 60° and these values lead to a helical structure with a pitch of 34 Å and about ten nucleotide units per turn of the helix. The proposed models of Watson & Crick, DNA-B and DNA-C lie in high energy regions.

Conformation of 2,3-diformylglycerol, a model compound of membrane phospholipids

The conformations of 2,3-diformylglycerol, a model compound of the diacylglycerol portion of phospholipids, were analyzed both by the classical potential function method and by the INDO molecular orbital method. The results suggest that in membranes, the conformation of the diacylglycerol portion of phospholipids is such that the two ester planes of the β- and γ-hydrocarbon chains stack in an antiparallel way with the dihedral angles β′{C(3)C(2)O(21)C(21)} ≅ 270° and γ 1{C(2)C(3)O(31)C(31)} ≅ 270°.

Conformational studies of ethylene glycol and its two methyl ether derivatives

As a theoretical analysis of the conformational equilibria of ethylene glycol, methoxyethanol and dimethoxyethane, the energy of each stable conformational isomer (rotamer) of these molecules was calculated for various temperatures and solvent dielectric constants. Classical semi-empirical potential functions were used. Besides intrinsic potentials for rotation about single bonds, intramolecular dispersion and repulsive interaction, dipole-dipole interaction and hydrogen bonding energies were included. Interaction with the solvent was considered only in terms of a continuous dielectric medium interacting with the local dipoles and quadrupoles of the molecule. For each rotamer, the dihedral angles giving the lowest energy were determined. From the energies of each rotamer, Boltzmann distributions of populations were obtained, and total concentrations were calculated in various physically distinguishable states, e.g. those with and without internal hydrogen bonds, or those in which the central C-C bond takes a trans or a gauche conformation. It is shown that the equilibrium constants, K HB and K TG, for these two cases are not identical. While changes in the dielectric constant may alter strongly the geometries and energies of individual rotamers, their effect on the average geometries and on the two equilibrium constants is small. The same is true of temperature changes, and is due to the presence of several rotamers in each of the physical states considered. Thus the small temperature dependence of some observed physical properties is shown to be consistent with the distribution of molecules over several conformational states. In solution, the fraction of ethylene glycol molecules with two free OH groups (i.e. without an intramolecular hydrogen bond) is predicted to be at least 20 per cent. This shows that the presence of three-dimensional hydrogen-bonded structures in the liquid, which we propose, is possible in principle.

Stereochemistry of cytidine: conformational analysis and hydrogen bonding

The energy calculations using the INDO molecular orbital method and classical potential function show that the syn conformation of pyrimidine nucleosides having the C (2')-endo or C (2')-endo-C (3')-endo sugar ring puckering is as stable as the corresponding anti form. The O (2')-O (2') base-ribose hydrogen bonding significantly alters the Φ CN conformation by confining the allowed Φ CN ranges to about 150–210°.

Quantum chemical studies on the conformational structure of nucleic acids I. Extended Hückel calculations on d-ribose phosphate

The extended Mickel theory has been used to predict the stable conformations of d-ribose phosphate. The results have been compared with those obtained from “contact criterion” and from classical potential functions.

Effect of prednisolone in Bancroftian elephantiasis.

Molecular orbital calculations and classical potential function calculations were carried out to examine the proposal that the conformations of the hallucinogenic tryptamines and phenylalkylamines are such that their 6-membered aromatic rings and their alkylamino nitrogens are congruent with A ring and N(6) nitrogen atom of lysergic acid diethylamide (the nitrogen of the D ring). The congruent conformation of psilocin is Ψ{C(9)-C(3)-C(β)-C(α)} = 46 ± 10 degrees, φ{C(3)-C(β)-C(α)-N} = 230 ± 20 degrees, θ₁{C(β)-C(α)-N-C(1N)} = 180 ± 10 degrees, and θ₂{C(β)-C(α)-N-C(2N)} = 300 ± 10 degrees; that of mescaline is ψ{C(2)-C(1)-C(β)-C(α) = 147 ± 10 degrees and φ{C(l)-C[β]-C(α)-N} = 160 ± 20 degrees. These results show that congruence of psilocin and mescaline with lysergic acid diethylamide is energetically permissible.