Conformational Degrees Of Freedom Research Articles

Charge Transport in Single Au | Alkanedithiol | Au Junctions: Coordination Geometries and Conformational Degrees of Freedom

Recent STM molecular break-junction experiments have revealed multiple series of peaks in the conductance histograms of alkanedithiols. To resolve a current controversy, we present here an in-depth study of charge transport properties of Au|alkanedithiol|Au junctions. Conductance histograms extracted from our STM measurements unambiguously confirm features showing more than one set of junction configurations. On the basis of quantum chemistry calculations, we propose that certain combinations of different sulfur-gold couplings and trans/gauche conformations act as the driving agents. The present study may have implications for experimental methodology: whenever conductances of different junction conformations are not statistically independent, the conductance histogram technique can exhibit a single series only, even though a much larger abundance of microscopic realizations exists.

Congenital Programs of the Behavior as the Unique Basis of the Brain Activity

The problem of adaptation of an organism to varying environmental conditions has been considered. It has been shown that an organism cannot learn if aprioristic information about an object is absent. The entire behavior of an organism is controlled by congenital programs. New programs of behavior do not appear during the lifetime of an organism. At the same time, the estimated quantity of information necessary for control of an organism shows that genes cannot contain all this information (the problem of the number of links between neurons and the problem of the number of antibodies). Models were proposed for the behavior control of organisms, in which the stores of the congenital information are (1) the complex internal structure of elementary particles and (2) conformational degrees of freedom of proteins (not coded by genes). In the first case, a particle may represent a quantum computer with many degrees of freedom. According to this model, biologically important molecules (DNA, nucleotides, and proteins) can change their state under the control of internal degrees of freedom of an elementary particle.

New amido derivatives as potential BKCa potassium channel activators. XI

The vasorelaxing effects of exogenous activators of large-conductance calcium-activated potassium channels (BK channels) can furnish the pharmacological rational basis for the treatment of hypertension and/or other diseases related with an impaired contractility of vessels. Since in previous works some benzanilide derivatives showed BK channel-induced vasorelaxing activity, in this paper we have taken into consideration the introduction of methylene spacer(s) between the amide linker and one or both the aromatic substituents, to evaluate the pharmacological effect caused by these lengthenings and to obtain possible useful information about structure–activity relationships. Overall, the main findings of this work suggest that the introduction of one or two methylene group(s) in the amide linker exerts a negative influence on the BK-opening properties, which can be due to an excessive lengthening of the spacer between the two aromatic rings and/or to further degrees of conformational freedom.

Physical model and the associative memory of a cytoskeleton microtubule as a system of dipoles

A physical model of the conformational degrees of freedom of a cytoskeleton microtubule represented as a system of interacting dipoles is elaborated, characteristic physical quantities are estimated, and a phase diagram of the ferroelectric state of the microtubule at T = 0 is constructed. The presence of frustrated couplings J ij between the dipoles appears to be the most important feature of the disordered dipole system of the microtubule, owing to which the ground state of the dipole system splits into a large number of lower energy states. The dynamics of the dipole system is determined by the relaxation of the dipole-dipole interaction energy. After the dipole system has evolved to its final state, the input image is associated with one of reference images stored earlier; hence, the dipole system of a microtubule can be viewed as a distributed system with associative memory.

Determination of Charge and Molecular Weight of Rigid-Rod Polyelectrolytes

Rod-like polyelectrolytes are an interesting model system because their persistence length is independent of the ionic strength and pH of the surrounding medium and they permit the investigation of polyelectrolytes in the absence of conformational degrees of freedom. In this work, rigid-rod poly(aramide) polyelectrolytes were synthesized by the Higashi method. Electrophoresis NMR spectroscopy in conjunction with diffusion NMR spectroscopy has been applied to determine the effective charge of the polymer. The charge was determined from the balance between the force in the electric field and the hydrodynamic friction in the steady-state electrophoretic motion. Because only organic counterions were present, and were identified in the proton NMR spectra, the counterions were investigated as well, and the fraction of condensed counterions was determined directly. From the effective charge per molecule and the knowledge of the fraction of condensed counterions, the total charge per molecule was determined. Finally, from the total charge, the number of repeat units and thus the molecular weight were inferred.

Matrix-Isolated Monomeric Tryptophan: Electrostatic Interactions as Nontrivial Factors Stabilizing Conformers

An extensive analysis of the conformational space of tryptophan (Trp) was performed at the B3LYP/6-311++G(d,p) level and verified by comparison with the infrared spectra of the compound isolated in low-temperature argon and xenon matrixes. Different types of conformers have been unequivocally identified in the matrixes. Type I exhibits the trans arrangement of the carboxylic group and is stabilized by an O-H...N intramolecular H-bond. Types II and III have the carboxylic group in the cis conformation and feature N-H...O=C and N-H...O-C hydrogen bonds, respectively. Three individual conformers of type I were identified in the matrixes. Other conformational degrees of freedom are related with the Calpha-Cbeta-Cgamma=C and C1-Calpha-Cbeta-Cgamma angles (chi1 and chi2, respectively). In proteins, these two dihedral angles define the conformations of the amino acid residues. In monomeric Trp, chi1 adopts the "+" (ca. +90 degrees ) and "-" (ca. -90 degrees ) orientations, while average values of -67.4, 170.5, and 67.6 degrees ("a", "b", and "c", respectively) were found for chi2. Theoretical analysis revealed two important factors in stabilizing the structures of the Trp conformers: the H-bond type and electrostatic interactions. Classified by the H-bond type, the most stable are forms I, followed by II and III. Out of possible combinations of the chi1 and chi2 dihedral angles, "a+", "b+", and "c-" were theoretically found more stable than their "a-", "b-", and "c+" counterparts. Thus, the stabilizing effect of interactions involving the pyrrole ring (which are possible in Ia+, Ib+, and Ic- conformers) is considerably higher compared to those in which the phenyl ring is engaged (existing in the Ia-, Ib-, and Ic+ forms).

Theoretical Characterization of α-Helix and β-Hairpin Folding Kinetics

By means of the conformational free energy surface and corresponding diffusion coefficients, as obtained by long time scale atomistic molecular dynamics simulations (mus time scale), we model the folding kinetics of alpha-helix and beta-hairpin peptides as a diffusive process over the free energy surface. The two model systems studied in this paper (the alpha-helical temporin L and the beta-hairpin prion protein H1 peptide) exhibit a funnel-like almost barrierless free energy profile, leading to nonexponential folding kinetics matching rather well the available experimental data. Moreover, using the free energy profile provided by Muñoz et al. [Muñoz et al. Nature 1997, 390: 196-199], this model was also applied to reproduce the two-state folding kinetics of the C-terminal beta-hairpin of protein GB1, yielding an exponential folding kinetics with a time constant (approximately 5 micros) in excellent agreement with the experimentally observed one (approximately 6 micros). Finally, the folding kinetics obtained by solving the diffusion equation, considering either a one-dimensional or a two-dimensional free energy surface, are also compared in order to understand the relevance of the possible kinetic coupling between conformational degrees of freedom in the folding process.

Parallel replica dynamics with a heterogeneous distribution of barriers: Application to n-hexadecane pyrolysis

Parallel replica dynamics simulation methods appropriate for the simulation of chemical reactions in molecular systems with many conformational degrees of freedom have been developed and applied to study the microsecond-scale pyrolysis of n-hexadecane in the temperature range of 2100-2500 K. The algorithm uses a transition detection scheme that is based on molecular topology, rather than energetic basins. This algorithm allows efficient parallelization of small systems even when using more processors than particles (in contrast to more traditional parallelization algorithms), and even when there are frequent conformational transitions (in contrast to previous implementations of the parallel replica algorithm). The parallel efficiency for pyrolysis initiation reactions was over 90% on 61 processors for this 50-atom system. The parallel replica dynamics technique results in reaction probabilities that are statistically indistinguishable from those obtained from direct molecular dynamics, under conditions where both are feasible, but allows simulations at temperatures as much as 1000 K lower than direct molecular dynamics simulations. The rate of initiation displayed Arrhenius behavior over the entire temperature range, with an activation energy and frequency factor of E(a) = 79.7 kcal/mol and log A/s(-1) = 14.8, respectively, in reasonable agreement with experiment and empirical kinetic models. Several interesting unimolecular reaction mechanisms were observed in simulations of the chain propagation reactions above 2000 K, which are not included in most coarse-grained kinetic models. More studies are needed in order to determine whether these mechanisms are experimentally relevant, or specific to the potential energy surface used.

Dynamics of nematics with conformational degrees of freedom

On the basis of Hamilton approach the dynamics of the biaxial nematics is considered. All hydrodynamic parameters, connected with broken symmetry, are introduced in terms of the distortion tensor. The equations of ideal hydrodynamics are obtained and the three spectra of collective excitations of biaxial nematics are considered, taking into account the rod-shape of molecules.

Self-assembly of flexible supramolecular metallacyclic ensembles: structures and adsorption properties of their nanoporous crystalline frameworks.

The syntheses, structures, and N2 adsorption properties of six new supramolecular metallacycles are reported. Flexible ditopic linkers, 1-4, with systematically varied lengths and conformational degrees of freedom were synthesized utilizing ester linkages. They were used in combination with (dppp)M(OTf)2, where M = Pt(II) and Pd(II), and cis-(Me3P)2Pt(OTf)2 to form flexible supramolecular metallacycles 5-10 in 88-98% isolated yields. Their structures were characterized via multinuclear NMR and X-ray crystallography. The metallacycles stack to form porous structures in the crystalline state. The pore dimensions depend on both the phosphorus ligands attached to the metals and the flexible linkers. Adsorption studies on the porous materials show that 5a, 6, 8, and 9 held 11.7, 16.5, 5.7, and 6.8 cm3/g STP of N2 at 77 K, respectively. A guest-exchange study with nitromethane and toluene reveals that the nanopore in 5 is flexible, a property which was transferred from the linker to the supramolecular structure in the solid state.

Dynamics of nematic liquid crystals with conformational degrees of freedom

AbstractOn the bases of the Hamilton approach the dynamics of the biaxial nematic are considered. The hydrodynamic parameters that are bound up with broken symmetry are introduced in terms of the distortion tensor. The density and flux density of additive integrals of motion are given in terms of energy density. The equations for ideal hydrodynamics are obtained and the spectra of collective excitations of biaxial nematics are considered taking into account the factor of the form of molecules. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

EVOLUTION OF A CATALYTICALLY EFFECTIVE MODEL ENZYME: THE IMPORTANCE OF TUNED CONFORMATIONAL FLUCTUATIONS

Possible causal connections between the dynamics of a thermally fluctuating model enzyme molecule and catalysis are explored. The model is motivated by observations from experiment and simulation that amino acid residues residing in different enzymatic domains may show markedly different degrees of conformational freedom. Consequently, we are interested in the catalytic efficacy of an enzyme as a function of long-range many-atom cooperative effects resulting from strong, moderate, and weak interactions between enzymatic residues. Here we show and quantify through molecular dynamics simulations how the number and distribution of these interactions affects an enzyme's conformational fluctuation dynamics and its effectiveness as a catalyst. For any given distribution of "stiff" and "loose" enzymatic domains, catalytic fitness is defined as the number of chemical events — specifically the number of times a catalytic residue and substrate surmount a chemical reaction barrier — during molecular dynamics simulation. Through mutation, recombination, and a selection procedure following the ideas of Darwinian evolution, a genetic algorithm drives a population of enzyme molecules to greater catalytic fitness by modifying the mix of stiff and loose interactions. Approximately 30,000 different enzyme molecules are generated by the genetic algorithm — each with a unique number and distribution of strong, moderate, and weak inter-residue interactions. While the catalytically least fit enzyme exhibits 16 chemical events, the fittest boasts 253. That point mutations far from the active-site chemistry in the fittest enzyme have a strong effect on the number of chemical events suggests that catalysis depends, in part, on long-range many-atom globally correlated dynamical fluctuations.

Spectral features of a nematic liquid crystal consisting of biaxial molecules with internal rotation

Expressions for the components of the optical permittivity tensor of a nematic liquid crystal consisting of biaxial π-conjugated molecules with a conformational degree of freedom (internal rotation) are obtained. A relationship between the intensity and dichroism of absorption bands in isotropic and nematic phases and the parameters of conformational, orientational, and mixed conformational and orientational orders of the molecules is established. A distribution function for the molecules is obtained that takes into account the mutual correlation of their conformational and orientational degrees of freedom. The effect of this correlation on the above-noted order parameters, the dichroism of the absorption bands, and the dependence of the measured oscillator strengths of molecular transitions on the character and degree of orientational order of biaxial molecules is studied. On the basis of comparison with experimental data, the relative role of different terms in the distribution function that are responsible for the correlation between the conformational and orientational degrees of freedom of the molecules is ascertained.

Phase behavior and concentration fluctuations in suspensions of hard spheres and nearly ideal polymers

The phase behavior and concentration fluctuations in suspensions of hard sphere colloids and nonadsorbing polymers under nearly ideal solvent conditions is studied experimentally. A remarkably different qualitative behavior compared to the athermal solvent case is observed for the dependence on polymer/particle size asymmetry of both the gelation and fluid–fluid phase separation boundaries. Near the theta state the effect of increasing the range of depletion attractions leads to a weak monotonic destabilization of the homogeneous phase at high particle volume fractions, with a reversal of the trend at lower volume fractions. In stark contrast to athermal solvent behavior, this nonmonotonic behavior results in multiple “curve crossings” of gel and phase separation boundaries as the polymer/particle size ratio is varied. Quantitative comparisons with no adjustable parameter PRISM integral equation theory for the fluid–fluid spinodals and osmotic compressibilities show good qualitative or semiquantitative agreement with all the experimental trends. The differences between good and ideal solvent conditions are largely attributed to changes in the polymer–polymer pair correlation functions due to the enhanced ability of coils to interpenetrate and cluster in theta solvents. Even for ideal solvent conditions the simplifying polymer model and statistical mechanical assumptions adopted by prior classic free volume and related approaches appear to miss fundamental aspects of the experimental behavior, especially for large size asymmetry ratios and/or moderate-to-high colloid volume fractions. The primary error can be identified with the approximation of a polymer chain by a phantom sphere with no conformational degrees of freedom.

X-ray crystal structures of D100E trichodiene synthase and its pyrophosphate complex reveal the basis for terpene product diversity.

The 2.4 A resolution X-ray crystal structure of D100E trichodiene synthase and the 2.6 A resolution structure of its complex with inorganic pyrophosphate are reported. The D100E amino acid substitution in the so-called "aspartate-rich" motif does not result in large changes to the overall structure of the enzyme. In the pyrophosphate complex, however, pyrophosphate coordinates two Mg(2+) ions at the mouth of the active site without causing large changes in the structure of the enzyme. This contrasts with pyrophosphate binding in the wild-type enzyme, where pyrophosphate coordinates three Mg(2+) ions and triggers a significant conformational change that closes the mouth of the active site and optimizes packing density in the enzyme-substrate complex. The attenuation of active site closure in D100E trichodiene synthase compromises enzyme-substrate packing density and confers additional spatial and conformational degrees of freedom on the substrate and carbocation intermediates, which in turn results in the formation of five alternate sesquiterpene products in addition to trichodiene. By extension, then, the diversity of terpene cyclases in biology may have evolved in part by amino acid substitutions that fine-tune structural changes dependent on metal-diphosphate complexation that govern the formation of the active site template and enzyme-substrate packing density.

Structure and Electronic Properties of Extended Chromophores for Applications in Second-Order Nonlinear Optics

A structural and theoretical analysis of new 2-[(4-phenylazo)phenyl] benzoxazole chromophores of potential interest in the field of second-order nonlinear optics is presented. Computations predict comparatively high hyperpolarizabilities for most of the compounds in their equilibrium nuclear configuration, with a significant dependence upon some conformational degrees of freedom and independence upon some others. This behavior is rationalized in the frame of the two-level model and sheds light on the conjugation pattern of these new chromophores.

Dichroism of absorption by impurity molecules with internal rotation in nematic liquid crystals

Expressions are obtained for the components of the permittivity tensor in the optical region for a nematic liquid crystal with impurity molecules having the internal rotation conformational degree of freedom. The dependence of the intensity and dichroism of the impurity absorption bands in isotropic and nematic phases on the parameters of conformational, orientation, and mixed conformation-orientation orders of molecules is found. The influence of the mutual correlation of conformational and orientation degrees of freedom of molecules on these parameters is studied. The dependence of the oscillator strengths of molecular transitions on the phase state of a medium and the orientation order of the impurity subsystem is analyzed. The self-consistent nature of molecular, structural, and spectral changes upon the nematic-isotropic liquid phase transition is demonstrated.

Flexible docking of peptide ligands to proteins.

Computer-simulated ligand binding or docking is a useful technique when studying intermolecular interactions or designing new pharmaceutical products. In general, the purpose of a docking experiment is twofold: (1) to find the most probable translational, rotational, and conformational juxtaposition of a given ligand-receptor pair, and (2) to evaluate the relative goodness-of-fit for different computed complexes. From a computational point of view, these are extremely difficult tasks and a satisfactory general solution to the docking problem has not yet been found. To explain this, let us consider the naïve approach in which a ligand is systematically moved relative to a given receptor. Here, the term “moved” must be understood as the combination of all possible translational, rotational, and conformational changes of the ligand. These operations define the so-called “docking box,” i.e., the a priori accessible phase space of the ligand, having dimensions 3+3+N (three translational, three rotational and N conformational degrees of freedom). While the six topological dimensions already seriously impede a docking simulation, the a priori conformational flexibility of the ligand and the receptor certainly poses the hardest (and least studied) problem. A large part of this chapter is devoted to a possible solution to this problem.

Asymmetry of the propagation of conformational excitations in a double-strand DNA molecule

A very simple model describing the conformational degrees of freedom of a double-strand DNA molecule is proposed. It is shown that the characteristic modes of the model consist of an acoustic (longitudinal with respect to the axis of the double helix) and two transverse optical modes. The latter modes are directly related with the deformations of the ideal structure of the double helix, which necessarily leads to softening of one of the optical modes on a finite wave vector. It is found that the conformational excitations propagating in DNA are asymmetric.

Conformational Coverage by a Genetic Algorithm

A new approach for coverage of the conformational space by a limited number of conformers is proposed. Instead of using a systematic search whose time complexity increases exponentially with degrees of freedom, a genetic algorithm (GA) is employed to minimize 3D similarity among the conformers generated. This makes the problem computationally feasible even for large, flexible molecules. The 3D similarity of a pair of conformers is assumed to be reciprocal to the root-mean-square (rms) distance between identical atomic sites in an alignment providing its minimum. Thus, in contrast to traditional GA, the fitness of a conformer is not quantified individually but only in conjunction with the population it belongs to. The approach handles the following stereochemical and conformational degrees of freedom: rotation around acyclic single and double bonds, inversion of stereocenters, flip of free corners in saturated rings, and reflection of pyramids on the junction of two or three saturated rings. The latter tw...