Topology of cyclo-octane energy landscape.
Ontology highlight
ABSTRACT:
SUBMITTER: Martin S
PROVIDER: S-EPMC3188624 | biostudies-other | 2010 Jun
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Assemblies of structural maintenance of chromosomes (SMC) proteins and kleisin subunits are essential to chromosome organization and segregation across all kingdoms of life. While structural data exist for parts of the SMC-kleisin complexes, complete structures of the entire complexes have yet to be determined, making mechanistic studies difficult. Using an integrative approach that combines crystallographic structural information about the globular subdomains, along with coevolutionary information and an energy landscape optimized force field (AWSEM), we predict atomic-scale structures for several tripartite SMC-kleisin complexes, including prokaryotic condensin, eukaryotic cohesin, and eukaryotic condensin. The molecular dynamics simulations of the SMC-kleisin protein complexes suggest that these complexes exist as a broad conformational ensemble that is made up of different topological isomers. The simulations suggest a critical role for the SMC coiled-coil regions, where the coils intertwine with various linking numbers. The twist and writhe of these braided coils are coupled with the motion of the SMC head domains, suggesting that the complexes may function as topological motors. Opening, closing, and translation along the DNA of the SMC-kleisin protein complexes would allow these motors to couple to the topology of DNA when DNA is entwined with the braided coils.
| S-EPMC6983425 | biostudies-literature
Project description:The asymmetric unit of the title compound (C6H14N2)[CdCl4]·H2O contained one 1,4-di-aza-bicyclo-[2.2.2]octane dication, a tetrahedral CdCl4 (2-) anion and a lattice water mol-ecule. In the crystal, the solvate water mol-ecule inter-acts with the cationic and anionic species via N-H?O and O-H?Cl [O?Cl = 3.289?(7)?Å] hydrogen-bond inter-actions, respectively, leading to a layered supramolecular structure extending parallel to (011).
| S-EPMC4011291 | biostudies-literature
Project description:We have investigated free energy landscape [MM/PBSA + normal modes entropy] of permutations in the G peptide (41-56) from the protein G B1 domain by studying six isomers corresponding to moving the hydrophobic cluster along the beta-strands (toward the turn: T1, AGEWTYDDKTFTVTET; T2, GEDTWDYATFTVTKTE; T3, GEDDWTYATFTVTKTE; toward the end: E1, WTYDDAGETKTFTVT; E2, WEYTGDDATKTETFTV; E3, WTYEGDDATKTETFTV). The free energy terms include molecular mechanics energy, Poisson-Boltzmann electrostatic solvation energy, surface area solvation energy, and conformational entropy estimated by using normal mode analysis. From the wild type to T1, then T3, and finally T2, we see a progressively changing energy landscape, toward a less stable beta-hairpin structure. Moving the hydrophobic cluster outside toward the end region causes a greater change in the energy landscape. alpha-Helical instead of a beta-hairpin structure was the most stable form for the E2 isomer. However, no matter how much the sequence changes, for all variants studied, ideal "native" beta-hairpin topologies remain as minima (regardless of whether global or local) in the energy landscape. In general, we find that the energy landscape is dependent on the hydrophobic cluster topology and on the sequence. Our present study indicates that the key is the relative conformational energies of the different conformations. Changes in the sequence strongly modulate the relative stabilities of topologically similar regions in the energy landscape, rather than redefine the topology space. This finding is consistent with a population redistribution in the process of protein folding. The limited variation of topological space, compared with the number of possible sequence changes, may relate to the observation that the number of known protein folds are far less than the sequential allowance.
| S-EPMC2323986 | biostudies-literature
Project description:While ubiquitous, energy redistribution remains a poorly understood facet of the nonequilibrium thermodynamics of biomolecules. At the molecular level, finite-size effects, pronounced nonlinearities, and ballistic processes produce behavior that diverges from the macroscale. Here, we show that transient thermal transport reflects macromolecular energy landscape architecture through the topological characteristics of molecular contacts and the nonlinear processes that mediate dynamics. While the former determines transport pathways via pairwise interactions, the latter reflects frustration within the landscape for local conformational rearrangements. Unlike transport through small-molecule systems, such as alkanes, nonlinearity dominates over coherent processes at even quite short time- and length-scales. Our exhaustive all-atom simulations and novel local-in-time and space analysis, applicable to both theory and experiment, permit dissection of energy migration in biomolecules. The approach demonstrates that vibrational energy transport can probe otherwise inaccessible aspects of macromolecular dynamics and interactions that underly biological function.
| S-EPMC6789131 | biostudies-literature
Project description:Chromosome conformation capture experiments provide a rich set of data concerning the spatial organization of the genome. We use these data along with a maximum entropy approach to derive a least-biased effective energy landscape for the chromosome. Simulations of the ensemble of chromosome conformations based on the resulting information theoretic landscape not only accurately reproduce experimental contact probabilities, but also provide a picture of chromosome dynamics and topology. The topology of the simulated chromosomes is probed by computing the distribution of their knot invariants. The simulated chromosome structures are largely free of knots. Topologically associating domains are shown to be crucial for establishing these knotless structures. The simulated chromosome conformations exhibit a tendency to form fibril-like structures like those observed via light microscopy. The topologically associating domains of the interphase chromosome exhibit multistability with varying liquid crystalline ordering that may allow discrete unfolding events and the landscape is locally funneled toward "ideal" chromosome structures that represent hierarchical fibrils of fibrils.
| S-EPMC4434716 | biostudies-literature
Project description:Reduction of bi-cyclo-[3.3.0]octane-3,7-dione yields a mixture of the endo-3,endo-7-diol and endo-3, exo-7-diol (C8H14O2) isomers (5 and 6). These form (5)2·(6) co-crystals in the monoclinic P21/n space group (with Z = 6, Z' = 1.5) rather than undergoing separation by means of fractional recrystallization or column chromatography. The mol-ecule of 5 occupies a general position, whereas the mol-ecule of 6 is disordered over two orientations across a centre of symmetry with occupancies of 0.463 (2) and 0.037 (2). Individual diol hy-droxy groups associate around a pseudo-threefold screw axis by means of hydrogen bonding. The second hy-droxy group of each diol behaves in a similar manner, generating a three-dimensional hydrogen-bonded network structure. This hydrogen-bond connectivity is identical to that present in three known helical tubuland diol-hydro-quinone co-crystals, and the new crystal structure is even more similar to two homologous aliphatic diol co-crystals.
| S-EPMC8061109 | biostudies-literature
Project description:In the structure of the binuclear title compound, [Cd2(C6H13N2)2Cl6], two Cd(II) atoms are bridged by two Cl(-) ligands, defining a centrosymmetric Cd2Cl2 motif. Each metal cation is additionally coordinated by two Cl(-) ligands and the N atom of a protonated 1,4-di-aza-bicyclo-[2.2.2]octane (H-DABCO)(+) ligand, leading to an overall trigonal-bipyramidal coordination environment with one of the bridging Cl(-) ligands and the N atom at the apical sites. In the crystal, the neutral dimers are linked via N-H?Cl hydrogen bonds, forming a two-dimensional network expanding parallel to (100).
| S-EPMC4719863 | biostudies-literature
Project description:Personalized anticancer therapy requires continuous consolidation of emerging bioinformatics data into meaningful and accurate information streams. The use of novel mathematical and physical approaches, namely topology and thermodynamics can enable merging differing data types for improved accuracy in selecting therapeutic targets. We describe a method that uses chemical thermodynamics and two topology measures to link RNA-seq data from individual patients with academically curated protein-protein interaction networks to select clinically relevant targets for treatment of low-grade glioma (LGG). We show that while these three histologically distinct tumor types (astrocytoma, oligoastrocytoma, and oligodendroglioma) may share potential therapeutic targets, the majority of patients would benefit from more individualized therapies. The method involves computing Gibbs free energy of the protein-protein interaction network and applying a topological filtration on the energy landscape to produce a subnetwork known as persistent homology. We then determine the most likely best target for therapeutic intervention using a topological measure of the network known as Betti number. We describe the algorithm and discuss its application to several patients.
| S-EPMC5386643 | biostudies-literature
Project description:Free-energy calculations play an important role in the application of computational chemistry to a range of fields, including protein biochemistry, rational drug design, or materials science. Importantly, the free-energy difference is directly related to experimentally measurable quantities such as partition and adsorption coefficients, water activity, and binding affinities. Among several techniques aimed at predicting free-energy differences, perturbation approaches, involving the alchemical transformation of one molecule into another through intermediate states, stand out as rigorous methods based on statistical mechanics. However, despite the importance of free-energy calculations, the applicability of the perturbation approaches is still largely impeded by a number of challenges, including the definition of the perturbation path, i.e., alchemical changes leading to the transformation of one molecule to the other. To address this, an automatic perturbation topology builder based on a graph-matching algorithm is developed, which can identify the maximum common substructure (MCS) of two or multiple molecules and provide the perturbation topologies suitable for free-energy calculations using the GROMOS and the GROMACS simulation packages. Various MCS search options are presented leading to alternative definitions of the perturbation pathway. Moreover, perturbation topologies generated using the default multistate MCS search are used to calculate the changes in free energy between lysine and its two post-translational modifications, 3-methyllysine and acetyllysine. The pairwise free-energy calculations performed on this test system led to a cycle closure of 0.5 ± 0.3 and 0.2 ± 0.2 kJ mol-1, with GROMOS and GROMACS simulation packages, respectively. The same relative free energies between the three states are obtained by employing the enveloping distribution sampling (EDS) approach when compared to the pairwise perturbations. Importantly, this toolkit is made available online as an open-source Python package (https://github.com/drazen-petrov/SMArt).
| S-EPMC8479811 | biostudies-literature
Project description:The cyclo-P4 complexes [CpR Ta(CO)2 (?4 -P4 )] (CpR : Cp''=1,3-C5 H3 tBu2 , Cp'''=1,2,4-C5 H2 tBu3 ) turned out to be predestined for the formation of hollow spherical supramolecules with non-classical fullerene-like topology. The resulting assemblies constructed with CuX (X=Cl, Br) showed a highly symmetric 32-vertex core of solely four- and six-membered rings. In some supramolecules, the inner cavity was occupied by an additional CuX unit. On the other hand, using CuI, two different supramolecules with either peanut- or pear-like shapes and outer diameters in the range of 2-2.5?nm were isolated. Furthermore, the spherical supramolecules containing Cp''' ligands at tantalum are soluble in CH2 Cl2 . NMR spectroscopic investigations in solution revealed the formation of isomeric supramolecules owing to the steric hindrance caused by the third tBu group on the Cp''' ligand. In addition, a 2D coordination polymer was obtained and structurally characterized.
| S-EPMC5129560 | biostudies-literature