Finite element modeling of banded structures in Bombyx mori silk fibres.

Transmission electron microscopy studies have shown curved bands of contrast in degummed Bombyx mori fibres. This contrast implies a molecular difference between the light and dark bands, which in turn implies a periodic variation in mechanical properties along the fibre axis. Finite element modeling was used to compare the mechanical behaviour of fibres with various banded geometries. Lateral, longitudinal and diagonal lamellae were compared with V-shaped and parabolic cupped lamellae. The simulation results from the lamellar models were compared to laminar composite theory. The cupped parabolic and V-shaped geometrics both showed a redistribution of the axial stresses from the centre toward the edge of the fibre. This redistribution allowed for a substantial increase in the toughness compared to simple lateral lamella as well as a moderate increase in the initial modulus without a significant change in the yield strength.     

Finite element simulation of skeletal muscular structures obtained from images of histological serial sections

In this study, we present a method for the three-dimensional reconstruction of objects obtained from histological serial sections (exemplified by those of a pennate striated skeletal muscle) and its application to the finite element method. A hyperelastic material model is used for modeling biological soft tissue. The reconstruction process relies on the direct construction of a volumetric mesh using an octree approach which leads to a stable finite element method. Stability can be expressed in the spectral matrix condition number. To visualize stress patterns within the underlying anatomy the simulation results are projected onto images of the histological scenario.     

Half-sib mating structures

All ways in which all matings in a population can be between half-sibs under a generalization of regular systems of inbreeding are characterized for both finite and infinite populations. A model of random half-sib mating is developed and analyzed, and the asymptotic configuration of populations subject to it is described. The classical model of half-sib mating which ensues from the standard definition of regular systems of inbreeding is only one of many ways a population can propagate by half-sib mating, and a wide range of genetic identity is possible dependent on which half-sib mating structure governs a population.     

Adenovirus complex structures

Adenovirus has, for a long time, been a model system for understanding complex virus structure, assembly and interference in host cell processes. Recent structures of adenoviral capsid proteins critical for cell entry have given new insights into both interactions with host cell receptors and inter-capsid protein interactions, which determine the capsid architecture. Such studies are of importance in engineering adenovirus for use in various gene transfer applications. Remarkable and unexpected similarities have been revealed between the cell-attachment proteins and primary receptors of adenovirus and the unrelated reovirus, and between the capsid proteins and architecture of adenovirus, the enveloped bacteriophage PRD1 and other large DNA viruses.     

Pseudomorphic microbial structures

According to the recent data, carbonaceous chondrites occasionally have pseudomorphoses after microbes. The meteorite ages suggest that life had developed earlier than the Earth was formed.     

Protonated polynucleotide structures

The circular dichroism spectra of poly(dG). poly(dC) have been studied as a function of pH in 0.15 M NaCl solution. Acid titration to pH 2.5 showed two transitions, one around pH 5, the second below pH 3. These transitions are disproportionation reactions and are not due to the dissociation of the complexes. Alkaline back titration to neutrality showed only one step above pH 7, without appearance of the intermediate form. The hysteresis loop observed gave rise to a metastable (probably protonated) form at pH 7 which reverted to the neutral form upon heating or alkali treatment. In order to obtain again the metastable hysteretic form, a whole titration cycle to pH 2.5 had to be performed.Abbreviation CD circular dichroism Dedicated to Prof. A Janke (Vienna) on his 85th birthday.Part 13 is ref. [1].     

Modelling molecular structures

This paper gives a guided tour of the teaching programme on molecular modelling offered at the University of Manchester Institute of Science and Technology (UMIST) for first and second-year students. The article describes theory (mini-lectures and self-study projects), and problems that students are expected to tackle at the computer.     

Potassium channel structures

The molecular basis of K+ channel function is universally conserved. K+ channels allow K+ flux and are essential for the generation of electric current across excitable membranes. K+ channels are also the targets of various intracellular control mechanisms, such that the suboptimal regulation of channel function might be related to pathological conditions. Because of the fundamental role of K+ channels in controlling membrane excitability, a structural understanding of their function and regulation will provide a useful framework for understanding neuronal physiology. Many recent physiological and crystallographic studies have led to new insights into the workings of K+ channels.     

Selection Response in Finite Populations

Formulae were derived to predict genetic response under various selection schemes assuming an infinitesimal model. Account was taken of genetic drift, gametic (linkage) disequilibrium (Bulmer effect), inbreeding depression, common environmental variance, and both initial segregating variance within families (σ(AW0)(2)) and mutational (σ(M)(2)) variance. The cumulative response to selection until generation t(CR(t)) can be approximated as & where N(e) is the effective population size, σ(AW &)(2) = N(e)σ(M)(2) is the genetic variance within families at the steady state (or one-half the genic variance, which is unaffected by selection), and D is the inbreeding depression per unit of inbreeding. R(0) is the selection response at generation 0 assuming preselection so that the linkage disequilibrium effect has stabilized. β is the derivative of the logarithm of the asymptotic response with respect to the logarithm of the within-family genetic variance, i.e., their relative rate of change. R(0) is the major determinant of the short term selection response, but σ(M)(2), N(e) and β are also important for the long term. A selection method of high accuracy using family information gives a small N(e) and will lead to a larger response in the short term and a smaller response in the long term, utilizing mutation less efficiently.     

Assembly of protein tertiary structures from secondary structures using optimized potentials

We present a simulated annealing-based method for the prediction of the tertiary structures of proteins given knowledge of the secondary structure associated with each amino acid in the sequence. The backbone is represented in a detailed fashion whereas the sidechains and pairwise interactions are modeled in a simplified way, following the LINUS model of Srinivasan and Rose. A perceptron-based technique is used to optimize the interaction potentials for a training set of three proteins. For these proteins, the procedure is able to reproduce the tertiary structures to below 3 A in root mean square deviation (rmsd) from the PDB targets. We present the results of tests on twelve other proteins. For half of these, the lowest energy decoy has a rmsd from the native state below 6 A and, in 9 out of 12 cases, we obtain decoys whose rmsd from the native states are also well below 5 A.     

GPCR structures in drug design,emerging opportunities with new structures

In recent years, GPCR targets from diverse regions of phylogenetic space have been determined. This effort has culminated this year in the determination of representatives of all major classes of GPCRs (A, B, C, and F). Although much of the now well established knowledge on GPCR structures has been known for some years, the new high-resolution structures allow structural insight into the causes of ligand efficacy, biased signaling, and allosteric modulation. In this digest the structural basis for GPCR signaling in the light of the new structures is reviewed and the use of the new non-class A GPCRs for drug design is discussed.     

Intrapopulational differences of genome structures in two structures of salmon-like fishes

The natural populations of salmon-like catadromous fishes usually include several percents of residual (dwarf) forms, which are 10-15 times smaller than normal forms. A comparative investigation of normal and residual forms in two species: Oncorhynchus nerka and Salvelinus malma (Salmoniformes order) was made by means of DNA molecular hybridization technique. The essential differences in reassociation kinetics was detected in DNA from normal and residual forms of both species. The genome sizes (kinetic complexity) of normal and residual forms are approximately the same. But some families of repetitive nucleotide sequences are represented by considerably different amount of copies. Intrapopulational differences of genome structures of normal and residual forms in both species seem to be more rough in respect to reassociation kinetic than corresponding interspecies differences between malma and nerka. Comparative analyses and reassociation kinetics for long and shrt DNA fragments imply "xenopus type" of nucleotide sequence organization in both species which is common for the majority of animal and plant genomes investigated.     

Pseudopeptides and beta folding: x-ray structures compared with structures in solution

In order to restrain the flexibility of the peptide molecules and reduce their biodegradation, modifications of the main chain are now introduced in pseudopeptide analogues. Surprisingly, there is very little data on the conformational properties of these derivatives. We have examined pseudopeptide analogues of RCO-X-Y-NHR' model dipeptides in the depsi, N-methylated, reduced, retro, alpha, beta-dehydro, beta-amino acid, and hydrazino series, in the solid state by x-ray diffraction, and in solution by ir and 1H-nmr spectroscopy. This study provides us with accurate dimensions of the peptide surrogates, and gives some information on the conformational tendencies induced by these substitutions, with reference to those of the related dipeptide sequences.     

Prediction of structures of multidomain proteins from structures of the individual domains

We describe the development of a method for assembling structures of multidomain proteins from structures of isolated domains. The method consists of an initial low-resolution search in which the conformational space of the domain linker is explored using the Rosetta de novo structure prediction method, followed by a high-resolution search in which all atoms are treated explicitly and backbone and side chain degrees of freedom are simultaneously optimized. The method recapitulates, often with very high accuracy, the structures of existing multidomain proteins.     

Well-defined secondary structures.

Molecules and assemblies of molecules with well-defined secondary structures have been designed and characterized by controlling noncovalent interactions. By specifying intermolecular interactions, a class of information-storing molecular duplexes have been successfully developed. These H-bonded molecular duplexes demonstrate programmable, sequence-specificity and predictable, tunable stabilities. Based on these highly specific molecular zippers (or glues), a systematic approach to designing self-assembled structures is now feasible. Duplex-directed formation of beta-sheets, block copolymers and templated organic reactions have been realized. By specifying intramolecular noncovalent interactions, a backbone-rigidification strategy has been established, leading to unnatural molecular strands that adopt well-defined, crescent or helical conformations. The generality of this backbone-rigidification strategy has been demonstrated in three different classes of unnatural oligomers: oligoaramides, oligoureas and oligo(phenylene ethynylenes). Large nanosized cavities have been created based on the folding of these helical foldamers. Tuning the size of the nanocavities has been achieved without changing the underlying helical topology. These helical foldamers can serve as novel platforms for the systematic design of nanostructures.