A Molecular Dynamics Simulation of the FMN-RNA Aptamer Complex

Abstract: We report on an unrestrained molecular dynamics simulation of the FMN-RNA (flavin mononucleotide) aptamer. The simulated average structure maintains both cross-strand and intermolecular FMN-RNA NOEs from the NMR experiments and has all qualitative features of the NMR structure including the G10-U12-A25 base triple and the A13-G24, A8-G28 and G9-G27 mismatches. However, the relative orientation of the hairpin loop to the remaining part of the molecule differs from the NMR structure. The simulation predicts that the flexible phosphoglycerol part of FMN moves towards G27 and forms hydrogen bonds. There are structural long-lived water molecules in the FMN binding pocket forming hydrogen bonds within FMN and between FMN and RNA. In addition long-lived water is found bridging primarily RNA backbone atoms. A general feature of the environment of long-lived ‘structural ’ water are at least two and in most cases three or four potential acceptor atoms. The 2'-OH group of RNA usually acts as an acceptor in interactions with the solvent. There are almost no intra-strand O2’H(n)...O4’(n+1) hydrogen bonds within the RNA backbone. In the standard case the preferred orientation of the 2’-OH hydrogen atoms is approximately towards O3 ’ of the same nucleotide. However, a relatively large number o

Molecular modelling and footprinting studies of DNA minor groove binders: Bisquaternary ammonium heterocyclic compounds

We report new quantitative footprinting data which reveal differences in binding constants of bisquaternary ammonium heterocyclic compounds (BQA) with AT-rich DNA sites depending on the ligand structure and on size and sequence of the DNA binding site. In an attempt to understand the dependence of binding affinity on the ligand structure we have performed quantum-chemical AM1 calculations on the BQA compounds and on subunits to explore the conformational space and to calculate the electronic and structural features of individual ligand conformations. Due to the properties of the rotatable backbone bonds there is a large number of possible conformations with almost equal energy. We present a new method for the calculation of the radius of curvature of molecular structures. Assuming that strong binders should have a shape complementary to the DNA minor groove this measure is used to select the optimum conformations for DNA-drug binding. The approach yields the correct ligand conformation for SN6999, for which an X-ray DNA-drug structure is known. The curvature of the optimum conformations of all ligands is compared to the experimental binding constants. A correlation is found between curvature and binding constant provided other structural factors do not vary. Therefore, we conclude that within structurally similar BQA compounds the extent of curvature is the relevant quantity which modulates the binding affinity

Comparative analysis of the Borrelia garinii genome

Three members of the genus Borrelia (B.burgdorferi, B.garinii, B.afzelii) cause tick-borne borreliosis. Depending on the Borrelia species involved, the borreliosis differs in its clinical symptoms. Comparative genomics opens up a way to elucidate the underlying differences in Borrelia species. We analysed a low redundancy whole-genome shotgun (WGS) assembly of a B.garinii strain isolated from a patient with neuroborreliosis in comparison to the B.burgdorferi genome. This analysis reveals that most of the chromosome is conserved (92.7% identity on DNA as well as on amino acid level) in the two species, and no chromosomal rearrangement or larger insertions/deletions could be observed. Furthermore, two collinear plasmids (lp54 and cp26) seem to belong to the basic genome inventory of Borrelia species. These three collinear parts of the Borrelia genome encode 861 genes, which are orthologous in the two species examined. The majority of the genetic information of the other plasmids of B.burgdorferii is also present in B.garinii although orthology is not easy to define due to a high redundancy of the plasmid fraction. Yet, we did not find counterparts of the B.burgdorferi plasmids lp36 and lp38 or their respective gene repertoire in the B.garinii genome. Thus, phenotypic differences between the two species could be attributable to the presence or absence of these two plasmids as well as to the potentially positively selected genes

Study on the refrigerator bottom cabinet cavity acoustic behavior

Recently, sound comfort has become important in residential houses and noise emission is a distinctive feature for the selection of the home appliances in the same energy class. Refrigerators run continuously when it is compared with other home appliances. Therefore, reduction of refrigerator noise is necessary and noise-free operation becomes the preferred choice of customers in the domestic refrigerators. Together with the fan, the compressor is a source of noise that contributes to most of the refrigerator’s overall noise level due to the existence of a rotary element and this element motion creates vibration and noise. In this study, acoustic behavior of bottom cabinet cavity, housing the compressor in a refrigerator, is investigated. The natural frequencies of the bottom cabinet cavity are investigated. Firstly, natural frequencies are determined with analytical method. Secondly, natural frequencies are determined with numerical analysis using the finite element model of the bottom cabinet cavity. Comparisons with the results of the analytical study verify the validity of the numerical solution. Finally, experimental study is carried out for validation of both models. It is seen that the sound pressure of the bottom cabinet of the refrigerator is higher at some frequencies. These frequencies are in close match with the natural frequencies of the bottom cabinet cavity of the refrigerator which can be determined with the analytical and numerical analysis. For some peak frequencies, results into noise reduction by using sound absorber materials are also presented