Molecular Dynamics and Neutron Scattering Studies of Potassium Chloride in Aqueous Solution.

Neutron diffraction with isotopic substitution (NDIS) experiments were done on both natural abundance potassium and isotopically labeled KCl heavy water solutions to characterize the solvent structuring around the potassium ion in water. Preliminary measurements suggested that the literature value for the coherent neutron scattering length (2.69 fm) for K was significantly in error.

Molecular Dynamics and Neutron Scattering Studies of Mixed Solutions of Caffeine and Pyridine in Water.

Insight into the molecular interactions of homotactic and heterotactic association of caffeine and pyridine in aqueous solution is given on the basis of both experimental and simulation studies. Caffeine is about 5 times more soluble in a 3 m aqueous pyridine solution than it is in pure water (an increase from ∼0.1 m to 0.

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels.

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank.

Retro operation on the Trp-cage miniprotein sequence produces an unstructured molecule capable of folding similar to the original only upon 2,2,2-trifluoroethanol addition.

Amino acid sequence and environment are the most important factors determining the structure, stability and dynamics of proteins. To evaluate their roles in the process of folding, we studied a retroversion of the well-described Trp-cage miniprotein in water and 2,2,2-trifluoroethanol (TFE) solution. We show, by circular dichroism spectroscopy and nuclear magnetic resonance (NMR) measurement, that the molecule has no stable structure under conditions in which the Trp-cage is folded.

Basis Set Dependence of Interaction Energies Computed Using Composite Post-MP2 Methods.

We report the performance of composite post-MP2 ab initio methods with small basis sets for description of noncovalent interactions, using the S66 data set as a benchmark. For three representative complexes, it is shown that explicitly correlated coupled cluster (CCSD-F12a) methods yield interaction energies ca. 0.

Halogen bond tunability II: the varying roles of electrostatic and dispersion contributions to attraction in halogen bonds.

In a previous study we investigated the effects of aromatic fluorine substitution on the strengths of the halogen bonds in halobenzene…acetone complexes (halo = chloro, bromo, and iodo). In this work, we have examined the origins of these halogen bonds (excluding the iodo systems), more specifically, the relative contributions of electrostatic and dispersion forces in these interactions and how these contributions change when halogen σ-holes are modified. These studies have been carried out using density functional symmetry adapted perturbation theory (DFT-SAPT) and through analyses of intermolecular correlation energies and molecular electrostatic potentials.

Behavior of 4-hydroxynonenal in phospholipid membranes.

Under conditions of oxidative stress, 4-hydroxy-2-nonenal (4-HNE) is commonly present in vivo. This highly reactive and cytotoxic compound is generated by oxidation of lipids in membranes and can be easily transferred from a membrane to both cytosol and the extracellular space. Employing time-dependent fluorescence shift (TDFS) method and molecular dynamics simulations, we found that 4-HNE is stabilized in the carbonyl region of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer.

Counterion condensation in short cationic peptides: limiting mobilities beyond the Onsager-Fuoss theory.

We investigated the effect of the background electrolyte (BGE) anions on the electrophoretic mobilities of the cationic amino acids arginine and lysine and the polycationic peptides tetraarginine, tetralysine, nonaarginine, and nonalysine. BGEs composed of sodium chloride, sodium propane-1,3-disulfonate, and sodium sulfate were used. For the amino acids, determination of the limiting mobility by extrapolation, using the Onsager-Fuoss (OF) theory expression, yielded consistent estimates.

Robust and Efficient Constrained DFT Molecular Dynamics Approach for Biochemical Modeling.

Constrained density functional theory (cDFT) is a powerful tool to investigate the dynamics of the electrons accompanying various physical-chemical processes. In this article we present our recent progresses in the implementation of the method in the parallelized version of the DFT program deMon2k. We take advantage of the possibility to express atomic densities in terms of linear combination of Hermite Gaussian functions to improve the computation of the cDFT integration weights within the Hirshfeld and Voronoi deformation density electronic population approaches.

Advanced Corrections of Hydrogen Bonding and Dispersion for Semiempirical Quantum Mechanical Methods.

Semiempirical quantum mechanical methods with corrections for noncovalent interactions, namely dispersion and hydrogen bonds, reach an accuracy comparable to much more expensive methods while being applicable to very large systems (up to 10 000 atoms). These corrections have been successfully applied in computer-assisted drug design, where they significantly improve the correlation with the experimental data. Despite these successes, there are still several unresolved issues that limit the applicability of these methods.

Evaluation of the performance of post-Hartree-Fock methods in terms of intermolecular distance in noncovalent complexes.

Dissociation curves calculated using multiple correlated QM methods for 66 noncovalent complexes (Řezáč et al., J Chem Theory Comput 2011, 7, 2427) have allowed us to interpolate equilibrium intermolecular distances for each studied method. Comparison of these data with CCSD(T)/complete basis set reference geometries provides information on how these methods perform in geometry optimizations.

Chasing charge localization and chemical reactivity following photoionization in liquid water.

The ultrafast dynamics of the cationic hole formed in bulk liquid water following ionization is investigated by ab initio molecular dynamics simulations and an experimentally accessible signature is suggested that might be tracked by femtosecond pump-probe spectroscopy. This is one of the fastest fundamental processes occurring in radiation-induced chemistry in aqueous systems and biological tissue. However, unlike the excess electron formed in the same process, the nature and time evolution of the cationic hole has been hitherto little studied.

Arrhenius analysis of anisotropic surface self-diffusion on the prismatic facet of ice.

We present an Arrhenius analysis of self-diffusion on the prismatic surface of ice calculated from molecular dynamics simulations. The six-site water model of Nada and van der Eerden was used in combination with a structure-based criterion for determining the number of liquid-like molecules in the quasi-liquid layer. Simulated temperatures range from 230 K-287 K, the latter being just below the melting temperature of the model, 289 K.

Orientational dependence of the affinity of guanidinium ions to the water surface.

The behavior of guanidinium chloride at the surface of aqueous solutions is investigated using classical molecular dynamics (MD) simulations. It is found that the population of guanidinium ions oriented parallel to the interface is greater in the surface region than in bulk. The opposite is true for ions in other orientations.

Accurate description of argon and water adsorption on surfaces of graphene-based carbon allotropes.

Accurate interaction energies of nonpolar (argon) and polar (water) adsorbates with graphene-based carbon allotropes were calculated by means of a combined density functional theory (DFT)-ab initio computational scheme. The calculated interaction energy of argon with graphite (-9.7 kJ mol(-1)) is in excellent agreement with the available experimental data.

From a localized H3O radical to a delocalized H3O+···e- solvent-separated pair by sequential hydration.

The impact of microhydration on the electronic structure and reactivity of the H(3)O moiety is investigated by ab initio calculations. In the gas phase, H(3)O is a radical with spin density localized on its hydrogen end, which is only kinetically stable and readily decomposes into a water molecule and a hydrogen atom. When solvated by a single water molecule, H(3)O preserves to a large extent its radical character, however, two water molecules are already capable to shift most of the spin density to the solvent.

Like-charge guanidinium pairing from molecular dynamics and ab initio calculations.

Pairing of guanidinium moieties in water is explored by molecular dynamics simulations of short arginine-rich peptides and ab initio calculations of a pair of guanidinium ions in water clusters of increasing size. Molecular dynamics simulations show that, in an aqueous environment, the diarginine guanidinium like-charged ion pairing is sterically hindered, whereas in the Arg-Ala-Arg tripeptide, this pairing is significant. This result is supported by the survey of protein structure databases, where it is found that stacked arginine pairs in dipeptide fragments exist solely as being imposed by the protein structure.

Urea and guanidinium induced denaturation of a Trp-cage miniprotein.

Using a combination of experimental techniques (circular dichroism, differential scanning calorimetry, and NMR) and molecular dynamics simulations, we performed an extensive study of denaturation of the Trp-cage miniprotein by urea and guanidinium. The experiments, despite their different sensitivities to various aspects of the denaturation process, consistently point to simple, two-state unfolding process. Microsecond molecular dynamics simulations with a femtosecond time resolution allow us to unravel the detailed molecular mechanism of Trp-cage unfolding.

On the role of London dispersion forces in biomolecular structure determination.

A DNA dodecamer and the methyladenine···methylthymine (mA···mT) complex in aqueous environment have been studied by means of molecular dynamics simulation, with a modified force field accounting for the hypothetical absence of London dispersion forces. Under these conditions, the mA···mT complex is preserved, while the double-helical DNA oligomer passes via an extended, ladder-like intermediate to a collapsed structure. The results are interpreted in terms of stability and specificity of the structure of studied complexes.

Extrapolation and Scaling of the DFT-SAPT Interaction Energies toward the Basis Set Limit.

The dispersion energy term in the symmetry-adapted perturbation theory based on the density functional theory (DFT-SAPT) converges rather slowly with basis set size. Accurate results for large complexes, where only calculations in small basis sets are practical, can be obtained by extrapolation to the complete basis set limit (CBS). In this paper, we propose an extrapolation scheme with the variable exponent optimized specifically for the DFT-SAPT calculations in correlation-consistent basis sets with diffuse functions.

Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors.

A semiempirical quantum mechanical PM6-DH2 method accurately covering the dispersion interaction and H-bonding was used to score fifteen structurally diverse CDK2 inhibitors. The geometries of all the complexes were taken from the X-ray structures and were reoptimised by the PM6-DH2 method in continuum water. The total scoring function was constructed as an estimate of the binding free energy, i.

Effect of Water Polarizability on the Properties of Solutions of Polyvalent Ions: Simulations of Aqueous Sodium Sulfate with Different Force Fields.

We show that aqueous sodium sulfate solutions exhibit an unrealistically large degree of ion pairing and clustering when modeled using nonpolarizable force fields, with clusters resembling precipitate readily forming in a 0.5 m solution at ambient conditions. This aggregation behavior was found to be persistent in nonpolarizable water for a range of parameters of the sulfate anion.

Sequence-dependent configurational entropy change of DNA upon intercalation.

We investigated the intercalation of an antitumor drug ellipticine into four adenine-thymine (AT) rich DNA duplexes with the focus on the configurational entropy, by means of molecular dynamics (MD) simulations. Two possible binding orientations of ellipticine in a DNA double helix were studied, and the orientation with the pyrrole nitrogen exposed into a major groove was identified as the more probable. The configurational entropy change of DNA is shown to contribute significantly to the binding free energy.

A reliable docking/scoring scheme based on the semiempirical quantum mechanical PM6-DH2 method accurately covering dispersion and H-bonding: HIV-1 protease with 22 ligands.

In this study, we introduce a fast and reliable rescoring scheme for docked complexes based on a semiempirical quantum mechanical PM6-DH2 method. The method utilizes a PM6-based Hamiltonian with corrections for dispersion energy and hydrogen bonds. The total score is constructed as the sum of the PM6-DH2 interaction enthalpy, the empirical force field (AMBER) interaction entropy, and the sum of the deformation (PM6-DH2, SMD) and the desolvation (SMD) energies of the ligand.