Hydrophobic collapse in (in silico) protein folding

A model of hydrophobic collapse, which is treated as the driving force for protein folding, is presented. This model is the superposition of three models commonly used in protein structure prediction: (1) 'oil-drop' model introduced by Kauzmann, (2) a lattice model introduced to decrease the number of degrees of freedom for structural changes and (3) a model of the formation of hydrophobic core as a key feature in driving the folding of proteins. These three models together helped to develop the idea of a fuzzy-oil-drop as a model for an external force field of hydrophobic character mimicking the hydrophobicity-differentiated environment for hydrophobic collapse. All amino acids in the polypeptide interact pair-wise during the folding process (energy minimization procedure) and interact with the external hydrophobic force field defined by a three-dimensional Gaussian function. The value of the Gaussian function usually interpreted as a probability distribution is treated as a normalized hydrophobicity distribution, with its maximum in the center of the ellipsoid and decreasing proportionally with the distance versus the center. The fuzzy-oil-drop is elastic and changes its shape and size during the simulated folding procedure.     

Positive Solutions for Nonlinear Periodic Problems with the Scalar p-Laplacian

We study the existence of positive solutions for a nonlinear periodic problem driven by the scalar p-Laplacian and having a nonsmooth potential. We impose a nonuniform nonresonance condition at +?∞ and a uniform nonresonance condition at 0^?+?. Using degree theoretic argument based on a fixed point index for multifunctions, we prove the existence of a strict positive solution.     

Low-energy elementary surface excitations of symmetric films of liquid4He atT=0 K

It is known that low-energy elementary excitations of symmetric films of liquid⁴He atT=0 K are characterized by a momentum q parallel to the surface and may be described by bound states. We have evaluated wave functions and energies of these states for both best short-ranged and optimal long-ranged correlations. Quantities of physical interest may be expressed in terms of these eigenstates and, in particular, for very small momenta (q<0.2 Å^–1) they are mainly determined by the contribution due to the lowest-lying one. We propose analytic expressions for the lowest-lying excitations and fluctuations in the long-wavelength limit. It is proved that in this limiting case, the excitation energy _LW(q) and the averaged static structure functionS _LW(q) should go linearly to zero asq0, whereas the averaged direct correlationX _LW ^Dg (q) should diverge at the origin as 1/q. It is shown that numerical solutions exhibit the expected long-wavelength behavior provided that optimal correlations are used. All these results are displayed in a series of figures and are discussed in detail.     

Force-field parametrization and molecular dynamics simulations of Congo red

Congo red, a diazo dye widely used in medical diagnosis, is known to form supramolecular systems in solution. Such a supramolecular system may interact with various proteins. In order to examine the nature of such complexes empirical force field parameters for the Congo red molecule were developed. The parametrization of bonding terms closely followed the methodology used in the development of the charmm22 force field, except for the calculation of charges. Point charges were calculated from a fit to a quantum mechanically derived electrostatic potential using the CHELP-BOW method. Obtained parameters were tested in a series of molecular dynamics simulations of both a single molecule and a micelle composed of Congo red molecules. It is shown that newly developed parameters define a stable minimum on the hypersurface of the potential energy and crystal and ab initio geometries and rotational barriers are well reproduced. Furthermore, rotations around C-N bonds are similar to torsional vibrations observed in crystals of diphenyl-diazene, which confirms that the flexibility of the molecule is correct. Comparison of results obtained from micelles molecular dynamics simulations with experimental data shows that the thermal dependence of micelle creation is well reproduced.     

Synthesis of N‐[(tert‐Butoxy)carbonyl]‐3‐(9,10‐dihydro‐9‐oxoacridin‐2‐yl)‐L‐alanine,a New Fluorescent Amino Acid Derivative

A simple synthesis of a new, highly fluorescent amino acid and of its protected derivative useful in peptide studies is described. The obtained derivative, N‐[(tert‐butoxy)carbonyl]‐3‐(9,10‐dihydro‐9‐oxoacridin‐2‐yl)‐L ‐alanine ( 6 ), shows intense long‐wave absorption (above 360 nm) and emission (above 400 nm). The quantum yield of fluorescence of the investigated compound is very high, so it can serve as a sensitive analytical probe useful, e.g., in analysis of peptide conformations.     

Porphyrin system containing [2.2]paracyclophane units

Meso-tetrakis([2.2]paracyclophanyl)porphyrin was obtained from [2.2]paracyclophanecarbaldehyde and pyrrole. Replacement of phenyl groups in meso-tetraphenylporphyrin by paracyclophanyl substituents remarkably influences the electronic structure of the molecule, causing bathochromic shifts of all uv-vis absorption bands, and changing the ring current of the porphyrin core. The shifts in the electron spectrum are substantially greater than those observed for other porphyrin derivatives characterized by their extended π-electron systems, such as meso-tetrakis(2-phenylethenyl)porphyrin and meso-tetrakisbiphenylporphyrin.     

Genome-wide single-nucleotide polymorphism arrays demonstrate high fidelity of multiple displacement-based whole-genome amplification

Whole-genome DNA amplification by multiple displacement (MD-WGA) is a promising tool to obtain sufficient DNA amounts from samples of limited quantity. Using Affymetrix' GeneChip Human Mapping 10K Arrays, we investigated the accuracy and allele amplification bias in DNA samples subjected to MD-WGA. We observed an excellent concordance (99.95%) between single-nucleotide polymorphisms (SNPs) called both in the nonamplified and the corresponding amplified DNA. This concordance was only 0.01% lower than the intra-assay reproducibility of the genotyping technique used. However, MD-WGA failed to amplify an estimated 7% of polymorphic loci. Due to the algorithm used to call genotypes, this was detected only for heterozygous loci. We achieved a 4.3-fold reduction of noncalled SNPs by combining the results from two independent MD-WGA reactions. This indicated that inter-reaction variations rather than specific chromosomal loci reduced the efficiency of MD-WGA. Consistently, we detected no regions of reduced amplification, with the exception of several SNPs located near chromosomal ends. Altogether, despite a substantial loss of polymorphic sites, MD-WGA appears to be the current method of choice to amplify genomic DNA for array-based SNP analyses. The number of nonamplified loci can be substantially reduced by amplifying each DNA sample in duplicate.     

Effective cross-sections for molecular aggregation in external orienting fields

Effects of an external orienting field and orientational cross-section for molecular association on the kinetics of crystal nucleation and critical temperature of crystallization is discussed. Dipole and quadrupole effects of an electric (magnetic) field and quadrupole effects of hydrodynamic potential of uniaxial flow are considered. Critical temperature of crystallization, free energy barrier of nucleation and nucleation rates are orientation-dependent. Smaller orientational cross-sections result in stronger anisotropy of the nucleation rates.     

Surface photovoltage in semiconductors under sub-band-gap illumination: continuous distribution of surface states

Surface photovoltage spectra in semiconductors are analyzed when the sub-band-gap illumination induces the electron transitions from surface states to the conduction band under the assumption that distribution of surface states is continuous. From analysis performed it follows that the fictitious densities of surface states can be induced due to the wavelength dependence of the photoionization capture cross-section of surface states for electrons and by the electron recombination capture cross-section of surface states which depends on the energy position of surface states in the energy gap. The high illumination intensity (laser illumination), which makes completely empty the surface states, can eliminate the fictious surface states when the density of surface states is not very large, the temperature of measurements is low, and the surface potential barrier is high. Received: 24 June 1998 / Accepted: 29 March 1999 / Published online: 14 June 1999