Biomedical subjects

Tetyana V Bogdan

Publications and source records attributed to Tetyana V Bogdan.

4 recordsLinked to original sources

PubMed2006

Potential energy and free energy landscapes.

Familiar concepts for small molecules may require reinterpretation for larger systems. For example, rearrangements between geometrical isomers are usually considered in terms of transitions between the corresponding local minima on the underlying potential energy surface, V. However, transitions between bulk phases such as solid and liquid, or between the denatured and native states of a protein, are normally addressed in terms of free energy minima. To reestablish a connection with the potential energy surface we must think in terms of representative samples of local minima of V, from which a free energy surface is projected by averaging over most of the coordinates. The present contribution outlines how this connection can be developed into a tool for quantitative calculations. In particular, stepping between the local minima of V provides powerful methods for locating the global potential energy minimum, and for calculating global thermodynamic properties. When the transition states that link local minima are also sampled we can exploit statistical rate theory to obtain insight into global dynamics and rare events. Visualizing the potential energy landscape helps to explain how the network of local minima and transition states determines properties such as heat capacity features, which signify transitions between free energy minima. The organization of the landscape also reveals how certain systems can reliably locate particular structures on the experimental time scale from among an exponentially large number of local minima. Such directed searches not only enable proteins to overcome Levinthal's paradox but may also underlie the formation of "magic numbers" in molecular beams, the self-assembly of macromolecular structures, and crystallization.

Journal Article↗

PubMed2006

Equilibrium thermodynamics from basin-sampling.

We present a "basin-sampling" approach for calculation of the potential energy density of states for classical statistical models. It combines a Wang-Landau-type uniform sampling of local minima and a novel approach for approximating the relative contributions from local minima in terms of the volumes of basins of attraction. We have employed basin-sampling to study phase changes in atomic clusters modeled by the Lennard-Jones potential and for ionic clusters. The approach proves to be efficient for systems involving broken ergodicity and has allowed us to calculate converged heat capacity curves for systems that could previously only be treated using the harmonic superposition approximation. Benchmarks are also provided by comparison with parallel tempering and Wang-Landau simulations, where these proved feasible.

Journal Article↗

PubMed2004

New results for phase transitions from catastrophe theory.

Catastrophe theory predicts that in certain limits universal relations should exist between barrier heights, curvatures and the positions of local maxima and minima on a potential or free energy surface. In the present work we investigate these relations for both first- and second-order phase transitions, revealing that the ideal ratios often hold quite well over a wide range of conditions. This elementary catastrophe theory is illustrated for the melting transition of an atomic cluster, the isotropic-to-nematic transition in a liquid crystal, and the ferromagnetic-to-paramagnetic phase transition in the two-dimensional Ising model.

Journal Article↗

PubMed2003

Correlated ab initio study of nucleic acid bases and their tautomers in the gas phase, in a microhydrated environment and in aqueous solution. guanine: surprising stabilization of rare tautomers in aqueous solution.

Altogether eight keto and enol tautomers of guanine were studied theoretically in the gas phase, in a microhydrated environment (1 and 2 water molecules) and in bulk water. The structures of isolated, as well as mono- and dihydrated tautomers were determined by means of the RI-MP2 method using the extended TZVPP (5s3p2d1f/3s2p1d) basis set. The relative energies of isolated tautomers included the correction to higher correlation energy terms evaluated at the CCSD(T)/aug-cc-pVDZ level. The relative enthalpies at 0 K and relative free energies at 298 K were based on the above-mentioned relative energies and zero-point vibration energies, temperature-dependent enthalpy terms and entropies evaluated at the MP2/6-31G level. The keto form having hydrogen atom at N7 is the global minimum while the canonical form having hydrogen atom at N9 represents the first local minimum at all theoretical levels in vacuo and in the presence of 1 and 2 water molecules. All three unusual rare tautomers having hydrogens at N3 and N7, at N3 and N9, and also at N9 and N7 are systematically considerably less stable and can be hardly detected in the gas phase. The theoretical predictions fully agree with existing theoretical as well as experimental results. The effect of bulk solvent on the relative stability of guanine tautomers was studied by self-consistent reaction field and molecular dynamics free energy calculations using the thermodynamic integration method. Bulk solvent, surprisingly, strongly favored these three rare tautomers over all remaining low-energy tautomers and probably only these forms can exist in water phase. The global minimum (tautomer with hydrogens at N3 and N7) is by 13 kcal/mol more stable than the canonical form (3rd local minimum). Addition of one or two water molecules does not change the relative stability order of isolated guanine tautomers but the respective trend clearly supports the surprising stabilization of three rare forms.

Gases↗