Improving double-ended transition state searches for soft-matter systems.

Transitions between different stable configurations of biomolecules are important in understanding disease mechanisms, structure-function relations, and novel molecular-scale engineering. The corresponding pathways can be characterized efficiently using geometry optimization schemes based on double-ended transition state searches. An interpolation is first constructed between the known states and then refined, yielding a band that contains transition state candidates. Here, we analyze an example where various interpolation schemes lead to bands with a single step transition, but the correct pathway actually proceeds via an intervening, low-energy minimum. We compare a number of different interpolation schemes for this problem. We systematically alter the number of discrete images in the interpolations and the spring constants used in the optimization and test two schemes for adjusting the spring constants and image distribution, resulting in a total of 2760 different connection attempts. Our results confirm that optimized bands are not necessarily a good description of the transition pathways in themselves, and further refinement to actually converge transition states and establish their connectivity is required. We see an improvement in the optimized bands if we employ the adjustment of spring constants with doubly-nudged elastic band and a smaller improvement from the image redistribution. The example we consider is representative of numerous cases we have encountered in a wide variety of molecular and condensed matter systems

Energy Landscapes for Proteins: From Single Funnels to Multifunctional Systems

This report advances the hypothesis that multifunctional systems may be associated with multifunnel potential and free energy landscapes, with particular focus on biomolecules. It compares systems that exhibit single, double, and multiple competing structures, and contrasts multifunnel landscapes associated with misfolded amyloidogenic oligomers, which presumably do not arise as an evolutionary target. In this context, intrinsically disordered proteins could be considered intrinsically multifunctional molecules, associated with multifunnel landscapes. Potential energy landscape theory enables biomolecules to be treated in a common framework together with self‐organizing and multifunctional systems based on inorganic materials, atomic and molecular clusters, crystal polymorphs, and soft matter.epsr

Low Temperature Magnetic Properties of the Double Exchange Model

We study the {\it ferromagnetic} (FM) Kondo lattice model in the strong coupling limit (double exchange (DE) model). The DE mechanism proposed by Zener to explain ferromagnetism has unexpected properties when there is more than one itinerant electron. We find that, in general, the many-body ground state of the DE model is {\it not} globally FM ordered (except for special filled-shell cases). Also, the low energy excitations of this model are distinct from spin wave excitations in usual Heisenberg ferromagnets, which will result in unusual dynamic magnetic properties.Comment: 5 pages, RevTeX, 5 Postscript figures include

Relationship between homoeologous regulatory and structural genes in allopolyploid genome – A case study in bread wheat

<p>Abstract</p> <p>Background</p> <p>The patterns of expression of homoeologous genes in hexaploid bread wheat have been intensively studied in recent years, but the interaction between structural genes and their homoeologous regulatory genes remained unclear. The question was as to whether, in an allopolyploid, this interaction is genome-specific, or whether regulation cuts across genomes. The aim of the present study was cloning, sequence analysis, mapping and expression analysis of <it>F3H </it>(flavanone 3-hydroxylase – one of the key enzymes in the plant flavonoid biosynthesis pathway) homoeologues in bread wheat and study of the interaction between <it>F3H </it>and their regulatory genes homoeologues – <it>Rc </it>(red coleoptiles).</p> <p>Results</p> <p>PCR-based cloning of <it>F3H </it>sequences from hexaploid bread wheat (<it>Triticum aestivum </it>L.), a wild tetraploid wheat (<it>T. timopheevii</it>) and their putative diploid progenitors was employed to localize, physically map and analyse the expression of four distinct bread wheat <it>F3H </it>copies. Three of these form a homoeologous set, mapping to the chromosomes of homoeologous group 2; they are highly similar to one another at the structural and functional levels. However, the fourth copy is less homologous, and was not expressed in anthocyanin pigmented coleoptiles. The presence of dominant alleles at the <it>Rc-1 </it>homoeologous loci, which are responsible for anthocyanin pigmentation in the coleoptile, was correlated with <it>F3H </it>expression in pigmented coleoptiles. Each dominant <it>Rc-1 </it>allele affected the expression of the three <it>F3H </it>homoeologues equally, but the level of <it>F3H </it>expression was dependent on the identity of the dominant <it>Rc-1 </it>allele present. Thus, the homoeologous <it>Rc-1 </it>genes contribute more to functional divergence than do the structural <it>F3H </it>genes.</p> <p>Conclusion</p> <p>The lack of any genome-specific relationship between <it>F3H-1 </it>and <it>Rc-1 </it>implies an integrative evolutionary process among the three diploid genomes, following the formation of hexaploid wheat. Regulatory genes probably contribute more to the functional divergence between the wheat genomes than do the structural genes themselves. This is in line with the growing consensus which suggests that although heritable morphological traits are determined by the expression of structural genes, it is the regulatory genes which are the prime determinants of allelic identity.</p

Persistent Current in the Ferromagnetic Kondo Lattice Model

In this paper, we study the zero temperature persistent current in a ferromagnetic Kondo lattice model in the strong coupling limit. In this model, there are spontaneous spin textures at some values of the external magnetic flux. These spin textures contribute a geometric flux, which can induce an additional spontaneous persistent current. Since this spin texture changes with the external magnetic flux, we find that there is an anomalous persistent current in some region of magnetic flux: near Phi/Phi_0=0 for an even number of electrons and Phi/Phi_0=1/2 for an odd number of electrons.Comment: 6 RevTeX pages, 10 figures include

Finite temperature strong-coupling expansions for the Kondo lattice model

Strong-coupling expansions, to order $(t/J)^8$, are derived for the Kondo lattice model of strongly correlated electrons, in 1-, 2- and 3- dimensions at arbitrary temperature. Results are presented for the specific heat, and spin and charge susceptibilities.Comment: revtex

Breakdown of a conservation law in incommensurate systems

We show that invariance properties of the Lagrangian of an incommensurate system, as described by the Frenkel Kontorova model, imply the existence of a generalized angular momentum which is an integral of motion if the system remains floating. The behavior of this quantity can therefore monitor the character of the system as floating (when it is conserved) or locked (when it is not). We find that, during the dynamics, the non-linear couplings of our model cause parametric phonon excitations which lead to the appearance of Umklapp terms and to a sudden deviation of the generalized momentum from a constant value, signalling a dynamical transition from a floating to a pinned state. We point out that this transition is related but does not coincide with the onset of sliding friction which can take place when the system is still floating.Comment: 7 pages, 6 figures, typed with RevTex, submitted to Phys. Rev. E Replaced 27-03-2001: changes to text, minor revision of figure

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome

Background: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). Methods: We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Results: Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Conclusion: Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial