Dikeos Mario Soumpasis

Pair correlations in an NaCl-SPC water model simulations versus extended RISM computations.

The ten pair correlation functions characterizing the equilibrium structure of a simple electrolyte such as NaCl-water and previously obtained for a NaCl-SPC water model within the extended RISM framework are tested against molecular dynamics, constrained dynamics and Monte Carlo simulations employing Ewald and reaction field schemes for a high-temperature, highpressure thermodynamic state where all these approaches become simultaneously feasible. The O-O, H-H, Cl-O, and Na-Na RISM correlations are in good agreement with the simulation data. The Na-O, Na-H, and Na-Cl results agree in phase, but the RISM peaks are too small. Distinct differences in the position of the first peak are observed in the case of the O-H, Cl-H, and Cl-Cl pair correlations. These results provide evidence that the main reason for these discrepancies are the statistical approximations involved in the extended RISM scheme.

Computer simulation of aqueous Na-Cl electrolytes

The equilibrium structure of aqueous Na-Cl electrolytes in the concentration regime between 1 and 5 mol l-1 is studied by means of a molecular dynamics computer simulation using interaction-site descriptions of water and the ionic components. The electrostatic interactions are treated both with the newly developed charged-clouds scheme and with Ewald summation. In the case of a 5 mol l-1 electrolyte, the results for pair correlations obtained by the two methods are in excellent agreement. However, the charged-clouds technique is much faster than Ewald summation and makes simulations at lower salt concentrations feasible. It is found that both ion-water and ion-ion correlation functions depend only weakly on the ionic concentration. Sodium and chloride ions exhibit only a negligible tendency to form contact pairs. In particular, no chloride ion pairs in contact are observed.

Computer simulation do not support CL-CL pairing in aqueous NaCL solution

Ion-ion correlation functions of a 5M NaCl-SPC water model were calculated by molecular dynamics and Monte Carlo simulations. No paired anions were found in contradiction with the extended reference-interaction-site model theory predicting Cl-Cl pairs for the same model. In order to check for a possible water model dependence the transferable interacting point sites model was also considered. Calculations for a 5 M solution using molecular dynamics and for a single chloride pair in water using constrained molecular dynamics again did not show the formation of anion pairs in contact.

Hydration of nucleic acid fragments: comparison of theory and experiment for high-resolution crystal structures of RNA, DNA, and DNA-drug complexes.

A computationally efficient method to describe the organization of water around solvated biomolecules is presented. It is based on a statistical mechanical expression for the water-density distribution in terms of particle correlation functions. The method is applied to analyze the hydration of small nucleic acid molecules in the crystal environment, for which high-resolution x-ray crystal structures have been reported. Results for RNA [r(ApU).r(ApU)] and DNA [d(CpG).d(CpG) in Z form and with parallel strand orientation] and for DNA-drug complexes [d(CpG).d(CpG) with the drug proflavine intercalated] are described. A detailed comparison of theoretical and experimental data shows positional agreement for the experimentally observed water sites. The presented method can be used for refinement of the water structure in x-ray crystallography, hydration analysis of nuclear magnetic resonance structures, and theoretical modeling of biological macromolecules such as molecular docking studies. The speed of the computations allows hydration analyses of molecules of almost arbitrary size (tRNA, protein-nucleic acid complexes, etc.) in the crystal environment and in aqueous solution.

Correlations and free energies in restricted primitive model descriptions of electrolytes

The pair and triplet correlations of a restricted primitive model (RPM) description of aqueous NaCl solutions have been computed in the concentration regime 0.5–4 M via Monte Carlo simulations, using both the method of configuration statistics and the particle insertion (chemical potential) method. Comparison of the triplet data to Kirkwood’s superposition approximation and the Abe and convolution approximations shows that deviations occur only for distances close to contact. The entropy computed via the entropy expansion including terms up to third order and the insertion method is dominated essentially by packing effects. The pair correlations and thermodynamic properties derived from the simulations were compared to the hypernetted chain (HNC) approximation which was found to be very good corroborating the conclusions drawn from earlier RPM studies.

A statistical mechanical description of biomolecular hydration

An efficient and accurate theoretical description of the structural hydration of biological macromolecules is presented. The hydration of molecules of almost arbitrary size (tRNA, antibody-antigen complexes, photosynthetic reaction centre) can be studied in solution and in the crystalline environment. The biomolecular structure obtained from X-ray crystallography, NMR or modelling is required as input information. The structural arrangement of water molecules near a biomolecular surface is represented by the local water density, analogous to the corresponding electron density in an X-ray diffraction experiment. The water-density distribution is approximated in terms of two- and three-particle correlation functions of solute atoms with water using a potentials-of-mean-force expansion.

An extended RISM study of simple electrolytes: pair correlations in a NaCl-SPC water model

We have used the extended RISM approach in conjunction with the SPC model of water to compute the ten-pair correlation functions of aqueous NaCl systems in a wide range of salt concentrations (0–5 m). The numerical results are tested against experimental neutron scattering data and computer simulations wherever the latter are available and/or feasible. Overall the positions of the structural features in the correlation functions are reproduced quite well by the computation but other details such as some peak heights and the ion water coordination numbers obtained are less satisfactory. We discuss several problems encountered due to the assumptions inherent in the extended RISM approach one of which is the incorrect dielectric screening behaviour of this theory.

Hydration of an alpha-helical peptide: Comparison of theory and molecular dynamics simulation

We present a statistical mechanical description of biomolecular hydration that accurately describes the hydrophobic and hydrophilic hydration of a model α‐helical peptide. The local density of water molecules around a biomolecule is obtained by means of a potential‐of‐mean‐force (PMF) expansion in terms of pair‐ and triplet‐correlation functions of bulk water and dilute solutions of nonpolar atoms. The accuracy of the method is verified by comparing PMF results with the local density and site‐site correlation functions obtained by molecular dynamics simulations of a model α‐helix in solution. The PMF approach quantitatively reproduces all features of the peptide hydration determined from the molecular dynamics simulation. Regions of hydrophobic hydration near the Cα and Cβ atoms along the helix are well reproduced. The hydration of exposed polar groups at the N‐ and C‐termini of the helix are also well described by the theory. A detailed comparison of the local hydration by means of site‐site radial distribution functions evaluated with the PMF theory shows agreement with the molecular dynamics simulations. The formulation of this theory is general and can be applied to any biomolecular system. The accuracy, speed of computation, and local character of this theory make it especially suitable for studying large biomolecular systems.

A Rigorous Basepair Oriented Description of DNA Structures

We propose new, rigorous definitions for (i) basepair fixed coordinate systems and (ii) the twist, tilt, and roll angles (called tau, t, rho) describing the relative orientation of adjacent basepairs and bases in a pair, in arbitrary DNA structures obtained from x-ray diffraction, 2D NMR, or energy calculations. In contrast to the corresponding angular parameters (tg, theta T, theta R) and coordinate systems introduced by Dickerson and co-workers and currently in use, our angular parameters and coordinate systems, together with a set of three displacement parameters, dx, dy, dz, provide a mathematically correct and general description of DNA conformations at the basepairs and/or base level. For instance, our description is applicable when the DNA structure considered is inherently curved, irregular, and/or does not possess dyad (or pseudodyad) axes. We develop a computationally convenient algorithm for rigorous DNA conformational analysis and apply it to some of the known crystal structures. We establish the connection to the currently used parameters and test the consistency and efficiency of our methodology by reconstructing the Dickerson B dodecamer using only the sequence and the set of parameters obtained from the atomic coordinates. The six parameter (tau, t, rho, dx, dy, dz) basepair level reconstruction is good but not perfect. Perfect reconstruction is obtained when one also considers each base in a basepair (consideration of propeller twist alone is not sufficient). The variation of the rigorous parameters proposed along the sequence is much larger, but their average values agree with fiber and solution data much better than in the case of the currently used set. The results of our analysis do not support Trifonovs AA.TT wedge model for DNA curvature but provide some evidence in favor of the Crothers junction-bend model. We point out some of the limitations of basepair level approaches when applied to DNA structure prediction and quantitative understanding of sequence-dependent variations in structure.

B-Z DNA conformational transition in 1:1 electrolytes: dependence upon counterion size

We have studied the B‐Z transition of poly[d(G‐C)] in the presence of alkali metal, tetramethylammonium and tetraethylammonium chlorides at room temperature. The measured critical salt concentrations increase in the order Na, K, Rb, TMA, Cs and are in good agreement with the theoretical values predicted from a statistical‐mechanical treatment of the transition.