Heat conductivity of DNA double helix

Thermal conductivity of isolated single molecule DNA fragments is of importance for nanotechnology, but has not yet been measured experimentally. Theoretical estimates based on simplified (1D) models predict anomalously high thermal conductivity. To investigate thermal properties of single molecule DNA we have developed a 3D coarse-grained (CG) model that retains the realism of the full all-atom description, but is significantly more efficient. Within the proposed model each nucleotide is represented by 6 particles or grains; the grains interact via effective potentials inferred from classical molecular dynamics (MD) trajectories based on a well-established all-atom potential function. Comparisons of 10 ns long MD trajectories between the CG and the corresponding all-atom model show similar root-mean-square deviations from the canonical B-form DNA, and similar structural fluctuations. At the same time, the CG model is 10 to 100 times faster depending on the length of the DNA fragment in the simulation. Analysis of dispersion curves derived from the CG model yields longitudinal sound velocity and torsional stiffness in close agreement with existing experiments. The computational efficiency of the CG model makes it possible to calculate thermal conductivity of a single DNA molecule not yet available experimentally. For a uniform (polyG-polyC) DNA, the estimated conductivity coefficient is 0.3 W/mK which is half the value of thermal conductivity for water. This result is in stark contrast with estimates of thermal conductivity for simplified, effectively 1D chains ("beads on a spring") that predict anomalous (infinite) thermal conductivity. Thus, full 3D character of DNA double-helix retained in the proposed model appears to be essential for describing its thermal properties at a single molecule level.Comment: 16 pages, 12 figure

Two-phase stretching of molecular chains

While stretching of most polymer chains leads to rather featureless force-extension diagrams, some, notably DNA, exhibit non-trivial behavior with a distinct plateau region. Here we propose a unified theory that connects force-extension characteristics of the polymer chain with the convexity properties of the extension energy profile of its individual monomer subunits. Namely, if the effective monomer deformation energy as a function of its extension has a non-convex (concave up) region, the stretched polymer chain separates into two phases: the weakly and strongly stretched monomers. Simplified planar and 3D polymer models are used to illustrate the basic principles of the proposed model. Specifically, we show rigorously that when the secondary structure of a polymer is mostly due to weak non-covalent interactions, the stretching is two-phase, and the force-stretching diagram has the characteristic plateau. We then use realistic coarse-grained models to confirm the main findings and make direct connection to the microscopic structure of the monomers. We demostrate in detail how the two-phase scenario is realized in the \alpha-helix, and in DNA double helix. The predicted plateau parameters are consistent with single molecules experiments. Detailed analysis of DNA stretching demonstrates that breaking of Watson-Crick bonds is not necessary for the existence of the plateau, although some of the bonds do break as the double-helix extends at room temperature. The main strengths of the proposed theory are its generality and direct microscopic connection.Comment: 16 pges, 22 figure

Accuracy comparison of several common implicit solvent models and their implementations in the context of protein-ligand binding.

In this study several commonly used implicit solvent models are compared with respect to their accuracy of estimating solvation energies of small molecules and proteins, as well as desolvation penalty in protein-ligand binding. The test set consists of 19 small proteins, 104 small molecules, and 15 protein-ligand complexes. We compared predicted hydration energies of small molecules with their experimental values; the results of the solvation and desolvation energy calculations for small molecules, proteins and protein-ligand complexes in water were also compared with Thermodynamic Integration calculations based on TIP3P water model and Amber12 force field. The following implicit solvent (water) models considered here are: PCM (Polarized Continuum Model implemented in DISOLV and MCBHSOLV programs), GB (Generalized Born method implemented in DISOLV program, S-GB, and GBNSR6 stand-alone version), COSMO (COnductor-like Screening Model implemented in the DISOLV program and the MOPAC package) and the Poisson-Boltzmann model (implemented in the APBS program). Different parameterizations of the molecules were examined: we compared MMFF94 force field, Amber12 force field and the quantum-chemical semi-empirical PM7 method implemented in the MOPAC package. For small molecules, all of the implicit solvent models tested here yield high correlation coefficients (0.87-0.93) between the calculated solvation energies and the experimental values of hydration energies. For small molecules high correlation (0.82-0.97) with the explicit solvent energies is seen as well. On the other hand, estimated protein solvation energies and protein-ligand binding desolvation energies show substantial discrepancy (up to 10kcal/mol) with the explicit solvent reference. The correlation of polar protein solvation energies and protein-ligand desolvation energies with the corresponding explicit solvent results is 0.65-0.99 and 0.76-0.96 respectively, though this difference in correlations is caused more by different parameterization and less by methods and indicates the need for further improvement of implicit solvent models parameterization. Within the same parameterization, various implicit methods give practically the same correlation with results obtained in explicit solvent model for ligands and proteins: e.g. correlation values of polar ligand solvation energies and the corresponding energies in the frame of explicit solvent were 0.953-0.966 for the APBS program, the GBNSR6 program and all models used in the DISOLV program. The DISOLV program proved to be on a par with the other used programs in the case of proteins and ligands solvation energy calculation. However, the solution of the Poisson-Boltzmann equation (APBS program) and Generalized Born method (implemented in the GBNSR6 program) proved to be the most accurate in calculating the desolvation energies of complexes

SU(N) quantum spin models: A variational wavefunction study

The study of SU(N) quantum spin models is relevant to a variety of physical systems including ultracold atoms in optical lattices, and also leads to insights into novel quantum phases and phase transitions of SU(2) spin models. We use Gutzwiller projected fermionic variational wavefunctions to explore the phase diagram and correlation functions of SU(N) spin models in the self-conjugate representation, with Heisenberg bilinear and biquadratic interactions. In 1D, the variational phase diagram of the SU(4) spin chain is constructed by examining instabilities of the Gutzwiller projected free fermion ground state to various broken symmetries, and it agrees well with exact results.The spin and dimer correlations of the Gutzwiller projected free fermion state with N flavors of fermions are also in good agreement with exact and 1/N calculations for the critical points of SU(N) spin chains. In 2D, the variational phase diagram on the square lattice is obtained by studying instabilities of the Gutzwiller projected pi-flux state. The variational ground state of the pure Heisenberg model is found to exhibit long range Neel order for N=2,4 and spin Peierls order for N > 4. For N=4 and 6, biquadratic interactions lead to a complex phase diagram which includes an extended valence bond crystal in both cases, as well as a stable pi-flux phase for N=6. The spin correlations of the projected pi-flux state at N=4 are in good agreement with 1/N calculations. We find that this state also shows strongly enhanced dimer correlations, in qualitative accord with the large-N results. We compare our results with a recent QMC study of the SU(4) Heisenberg model.Comment: 22 pages, 7 figs, added references to arxiv versio

The role of chromosome-nuclear envelope attachments in 3D genome organization

Chromosomes are intricately folded and packaged in the cell nucleus and interact with the nuclear envelope. This complex nuclear architecture has a profound effect on how the genome works and how the cells function. The main goal of review is to highlight recent studies on the effect of chromosome–nuclear envelope interactions on chromatin folding and function in the nucleus. The data obtained suggest that chromosome–nuclear envelope attachments are important for the organization of nuclear architecture in various organisms. A combination of experimental cell biology methods with computational modeling offers a unique opportunity to explore the fundamental relationships between different aspects of 3D genome organization in greater details. This powerful interdisciplinary approach could reveal how the organization and function of the genome in the nuclear space is affected by the chromosome–nuclear envelope attachments and will enable the development of novel approaches to regulate gene expression