Protein sequence design on the basis of topology optimization techniques -Using continuous modeling of discrete amino acid types

The notion of optimization is inherent in protein design. A long linear chain of twenty types of amino acid residues are known to fold to a 3-D conformation that minimizes the combined inter-residue energy interactions. There are two distinct protein design problems, viz. predicting the folded structure from a given sequence of amino acid monomers (folding problem) and determining a sequence for a given folded structure (inverse folding problem). These two problems have much similarity to engineering structural analysis and structural optimization problems respectively. In the folding problem, a protein chain with a given sequence folds to a conformation, called a native state, which has a unique global minimum energy value when compared to all other unfolded conformations. This involves a search in the conformation space. This is somewhat akin to the principle of minimum potential energy that determines the deformed static equilibrium configuration of an elastic structure of given topology, shape, and size that is subjected to certain boundary conditions. In the inverse-folding problem, one has to design a sequence with some objectives (having a specific feature of the folded structure, docking with another protein, etc.) and constraints (sequence being fixed in some portion, a particular composition of amino acid types, etc.) while obtaining a sequence that would fold to the desired conformation satisfying the criteria of folding. This requires a search in the sequence space. This is similar to structural optimization in the design-variable space wherein a certain feature of structural response is optimized subject to some constraints while satisfying the governing static or dynamic equilibrium equations. Based on this similarity, in this work we apply the topology optimization methods to protein design, discuss modeling issues and present some initial results.

A one point shock capturing kinetic scheme for hyperbolic conservation laws

We have presented a new low dissipative kinetic scheme based on a modified Courant Splitting of the molecular velocity through a parameter φ. Conditions for the split fluxes derived based on equilibrium determine φ for a one point shock. It turns out that φ is a function of the Left and Right states to the shock and that these states should satisfy the Rankine-Hugoniot Jump condition. Hence φ is utilized in regions where the gradients are sufficiently high, and is switched to unity in smooth regions. Numerical results confirm a discrete shock structure with a single interior point when the shock is aligned with the grid.

Thermodynamics of GdMnO3 and GdMn2O5 phases determined by the EMF method

Using solid oxide galvanic cells of the type: MnO + Gd2O3 + GdMnO3/O-2/Ni + NiO and Mn3O4 + GdMnO3 + GdMn2O5/O-2/air the equilibrium oxygen pressure for the following reactions :MnO + 1/2Gd(2)O(3) + 1/4O(2) = GdMnO3 1/3Mn(3)O(4) + GdMnO3 + 1/3O(2) = GdMn2O5 was determined in the temperature range from 1073 to 1450 K. From the determined equilibrium oxygen partial pressure the corresponding G i b b s free energy change for these reactions was derived: Delta G(f,GdMnO3)(0) (+/- 425J) 132721(+/ - 2240) +51.91(+/ - 0.81)T Delta G(f,GdMn2O5)(0)(+/- 670J) 121858(+/ - 6176) + 79.52(+/ - 4.83)T From these data, standard G i b b s energies, enthalpies and entropies of formation of GdMnO3 and GdMn2O5 from component oxides and from the elements are derived. Thermodynamic data tables for the two ternary phases are compiled from 298.15 to 1400 K.

Effect of plasticizers on magnesium-poly(ethyleneoxide) polymer electrolyte

Solid polymer electrolytes (SPEs) of poly(ethyleneoxide) and magnesium triflate, which are plasticized with propylene carbonate (PC), ethylene carbonate (EC) and a mixture of PC and EC, are studied for their conductivity, ac impedance of the Mg I SPE interface, cyclic voltammetry, infrared spectroscopy and differential scanning calorimetry. in the presence of plasticizers, the ionic conductivity (a) increases from a value of 1 x 10(-8) S cm(-1) to about 1 x 10(-4) S cm(-1) at ambient temperature. The a is found to follow a VTF relationship with temperature. The values of the activation energy, pre-exponential factor and equilibrium glass transition temperature are shown to depend on the concentration of plasticizer. Ac impedance studies indicate lower interfacial impedance of Mg/plasticized SPE than stainless steel/plasticized SPE. The impedance spectra are analyzed using a non-linear least square curve fitting technique and the interfacial resistance of Mg/plasticized SPE is evaluated. The cyclic voltammetric results suggest a quasireversible type of Mg/Mg2+ couple in plasticized SPE. (C) 2000 Elsevier Science B.V. All rights reserved.

Molecular theory of solvation and solvation dynamics of a classical ion in a dipolar liquid

A microscopic theory of equilibrium solvation and solvation dynamics of a classical, polar, solute molecule in dipolar solvent is presented. Density functional theory is used to explicitly calculate the polarization structure around a solvated ion. The calculated solvent polarization structure is different from the continuum model prediction in several respects. The value of the polarization at the surface of the ion is less than the continuum value. The solvent polarization also exhibits small oscillations in space near the ion. We show that, under certain approximations, our linear equilibrium theory reduces to the nonlocal electrostatic theory, with the dielectric function (c(k)) of the liquid now wave vector (k) dependent. It is further shown that the nonlocal electrostatic estimate of solvation energy, with a microscopic c(k), is close to the estimate of linearized equilibrium theories of polar liquids. The study of solvation dynamics is based on a generalized Smoluchowski equation with a mean-field force term to take into account the effects of intermolecular interactions. This study incorporates the local distortion of the solvent structure near the ion and also the effects of the translational modes of the solvent molecules.The latter contribution, if significant, can considerably accelerate the relaxation of solvent polarization and can even give rise to a long time decay that agrees with the continuum model prediction. The significance of these results is discussed.

Solution cation-binding properties of segmented polyethylene oxide-A C-13 NMR spectroscopic study

Two segmented polyethylene oxides, SPEO-3 and SPEO-4, were prepared using a novel transetherification methodology. Their structures were confirmed by H-1 and C-13 NMR spectroscopy. The complexation of these SPEO's with alkali-metal ions in solution was investigated by C-13 NMR spectroscopy. The mole-fraction method was used to determine the complexation ratio of SPEO with LIClO4 at 25 degrees C, which showed that these formed 1:1 (polymer repeat unit/salt) complexes. The association constant, K, for the complex formation was calculated from the variation of the chemical shift values with salt concentration, using a standard nonlinear least-square fitting procedure. The maximum change in chemical shift (Delta delta) and the K values suggest that both SPEO-3 and SPEO-4 formed stronger complexes with lithium salts than with sodium salts. Unexpectedly, the K values were found to be different, when the variation of delta of different carbons was used in the fitting procedure. This suggests that several possible complexed species may be in equilibrium with the uncomplexed one. Structurally similar model compounds were also prepared and their complexation studies indicated that all of them also formed 1:1 complexes with Li salts. Interestingly, it was observed that the polymers gave higher K values suggesting the formation of more stable complexes in polymers when compared to the model analogues. (C) 2000 John Wiley & Sons, Inc.

Phase diagram and dielectric studies of binary organic materials

The phase equilibrium studies of organic system, involving resorcinol (R) and p-dimethylaminobenzaldehyde (DMAB), reveal the formation of a 1:1 molecular complex with two eutectics. The heat of mixing, entropy of fusion, roughness parameter, interfacial energy, and the excess thermodynamic functions were calculated based on enthalpy of fusion data determined via differential scanning calorimetric (DSC) method. X-ray powder diffraction studies confirm that the eutectics are not simple mechanical mixture of the components under investigation. The spectroscopic investigations (IR and NMR) suggest the occurrence of hydrogen bonding between the components forming the molecular complex. The dielectric measurements, carried out on hot-pressed addition compound (molecular complex), show higher dielectric constant at 320 K than that of individual components. The microstructural investigations of eutectic and addition compound indicate dendritic and faceted morphological features. (C) 2000 Elsevier Science B.V. All rights reserved.

Adhesion-Induced Instability in Asperities

Adhesive forces between two approaching asperities will deform the asperities, and under certain conditions this will result in a sudden runaway deformations leading to a jump-to-contact instability. We present finite element-based numerical studies on adhesion-induced deformation and instability in asperities. We consider the adhesive force acting on an asperity, when it is brought near a rigid half-space, due to van der Waals interaction between the asperity and the half-space. The adhesive force is considered to be distributed over the volume of the asperity (body force), thus resulting in more realistic simulations for the length scales considered. Iteration scheme based on a ``residual stress update'' algorithm is used to capture the effect of deformation on the adhesion force, and thereby the equilibrium configuration and the corresponding force. The numerical results are compared with the previous approximate analytical solutions for adhesion force, deformation of the asperity and adhesion-induced mechanical instability (jump-to-contact). It is observed that the instability can occur at separations much higher,and could possibly explain the higher value of instability separation observed in experiments. The stresses in asperities, particularly in case of small ones, are found to be high enough to cause yielding before jump -to-contact. The effect of roughness is considered by modeling a spherical protrusion on the hemispherical asperity.This small-scale roughness at the tip of the asperities is found to control the deformation behavior at small separations, and hence are important in determining the friction and wear due to the jump-to-contact instability.