The interaction of DNA with the polyamine spermine 4ϩ (Spm 4ϩ ), sodium ions, and water molecules has been studied using molecular dynamics computer simulations in a system modeling a DNA crystal. The simulation model consisted of three B-DNA decamers in a periodic hexagonal cell, containing 1200 water molecules, 8 Spm 4ϩ , 32 Na ϩ , and 4 Cl Ϫ ions. The present paper gives a more detailed account of a recently published report of this system and compares results on this mixed Spm 4ϩ /Na ϩ -cation system with an molecular dynamics simulation carried out for the same DNA decamer under similar conditions with only sodium counterions (Korolev et al., 2001, J. Mol. Biol. 308:907). The presence of Spm 4ϩ makes significant influence on the DNA hydration and on the interaction of the sodium ions with DNA. Spermine pushes water molecules out of the minor groove, whereas Na ϩ attracts and organizes water around DNA. The major binding site of the Spm 4ϩ amino groups and the Na ϩ ions is the phosphate group of DNA. The flexible polyamine spermine displays a high presence in the minor groove but does not form long-lived and structurally defined complexes. Sodium ions compete with Spm 4ϩ for binding to the DNA bases in the minor groove. Sodium ions also have several strong binding sites in the major groove. The ability of water molecules, Spm 4ϩ , and Na ϩ to modulate the local structure of the DNA double helix is discussed.

We report a detailed comparison between calculations of inter-filament interactions based on Monte-Carlo simulations and experimental features of lateral aggregation of bacteriophages fd and M13 induced by a number of divalent metal ions. The general findings are consistent with the polyelectrolyte nature of the virus filaments and confirm that the solution electrostatics account for most of the experimental features observed. One particularly interesting discovery is resolubilization for bundles of either fd or M13 viruses when the concentration of the bundle-inducing metal ion Mg(2+) or Ca(2+) is increased to large (>100 mM) values. In the range of Mg(2+) or Ca(2+) concentrations where large bundles of the virus filaments are formed, the optimal attractive interaction energy between the virus filaments is estimated to be on the order of 0.01 kT per net charge on the virus surface when a recent analytical prediction to the experimentally defined conditions of resolubilization is applied. We also observed qualitatively distinct behavior between the alkali-earth metal ions and the divalent transition metal ions in their action on the charged viruses. The understanding of metal ions-induced reversible aggregation based on solution electrostatics may lead to potential applications in molecular biology and medicine.

Molecular dynamics simulations of the [d(ATGCAGTCAG]2 fragment of DNA, in water and in the presence of three different counter-ions (Li+, Na+ and Cs+) are reported. Three-dimensional hydration structure and ion distribution have been calculated using spatial distribution functions for a detailed picture of local concentrations of ions and water molecules around DNA. According to the simulations, Cs+ ions bind directly to the bases in the minor groove, Na+ ions bind prevailing to the bases in the minor groove through one water molecule, whereas Li+ ions bind directly to the phosphate oxygens. The different behavior of the counter-ions is explained by specific hydration structures around the DNA and the ions. It is proposed how the observed differences in the ion binding to DNA may explain different conformational behavior of DNA. Calculated self-diffusion coefficients for the ions agree well with the available NMR data.

With the rapid development of computer power and wide availability of modelling software computer simulations of realistic models of lipid membranes, including their interactions with various molecular species, polypeptides and membrane proteins have become feasible for many research groups. The crucial issue of the reliability of such simulations is the quality of the force field, and many efforts, especially in the latest several years, have been devoted to parametrization and optimization of the force fields for biomembrane modelling. In this review, we give account of the recent development in this area, covering different classes of force fields, principles of the force field parametrization, comparison of the force fields, and their experimental validation. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg.

Atomistic force field parameters were developed for the TiO 2 −water interface by systematic optimization with respect to experimentally determined crystal structures (lattice parameters) and surface thermodynamics (water adsorption enthalpy). Optimized force field parameters were determined for the two cases where TiO 2 was modeled with or without covalent bonding. The nonbonded TiO 2 model can be used to simulate different TiO 2 phases, while the bonded TiO 2 model is particularly useful for simulations of nanosized TiO 2 and biomatter, including protein− surface and nanoparticle−biomembrane simulations. The procedure is easily generalized to parametrize interactions between other inorganic surfaces and biomolecules. ■ INTRODUCTIONBiomolecules interacting with inorganic objects are fundamental in nanobiotechnological applications such as surfaceattached biomolecules for target delivery of drug molecules, 1 protein adsorption to medical implants, 2 protein−nanoparticle interactions 3 and, not least, to understand the molecular mechanisms of nanotoxicity. 4 The contact points between inorganic surfaces and biomatter (the nanobio interface 5 ) can be tracked with experimental techniques like dynamic light scattering (DLS), 6−8 chromatography 9,10 and/or spectroscopy, 11,12 but only by indirect measurements.On the other hand, computer simulations can in principle be used to directly calculate interactions at the nanobio interface, covering system sizes ∼1000 Å and time scales ∼1000 ns. These windows are highly relevant when modeling the nanobio interface, but outside the realm of quantum mechanics. This calls for "classical" models with atomistic or semiatomistic (atoms being grouped into effective interaction centers) representations in computer simulations of nanobio interactions, parametrized to reproduce properties relevant to the nanobio interface. Substantial effort has been invested during the last decades to develop classical molecular models for biomolecules (proteins, lipids, nucleic acids, carbohydrates, etc.), but there has been no comparable endeavor to include inorganic materials into the models. The state of classical models aimed to describe the nanobio interface remains underdeveloped, largely because of the difficulties involved with representing the electronic structure of the inorganic material by interacting point particles. The present work is an attempt to close this modeling gap by developing atomistic force field parameters for the TiO 2 −water interface. We use an automated algorithm that is extended to accept arbitrary experimental data as targets in the parameter fitting. The method can easily be generalized to develop force field parameters for other inorganic surfaces and biomolecules. In an accompanying paper, 13 we use the optimized force field parameters to address the other long-standing problem in nanobio simulationsaccurate sampling of biomolecules near inorganic surfacesand to compute binding free energies of amino acid side chain analogues and a peptide to the TiO 2 surface.T...

In this work we propose a new force field for modelling of adsorption of CO2, N2, O2 and Ar in all silica and Na+ exchanged Si–Al zeolites. The force field has a standard molecular-mechanical functional form with electrostatic and Lennard-Jones interactions satisfying Lorentz–Berthelot mixing rules and thus has a potential for further extension in terms of new molecular types. The parameters for the zeolite framework atom types are optimized by an iterative procedure minimizing the difference with experimental adsorption data for a number of different zeolite structures and Si:Al ratios. The new force field shows a good agreement with available experimental data including those not used in the optimization procedure, and which also shows a reasonable transferability within different zeolite topologies. We suggest a potential usage in screening of different zeolite structures for carbon capture and storage process, and more generally, for separation of other gases.

Numerical calculations, using Poisson-Boltzmann (PB) and counterion condensation (CC) polyelectrolyte theories, of the electrostatic free energy difference, DeltaGel, between single-stranded (coil) and double-helical DNA have been performed for solutions of NaDNA + NaCl with and without added MgCl2. Calculations have been made for conditions relevant to systems where experimental values of helix coil transition temperature (Tm) and other thermodynamic quantities have been measured. Comparison with experimental data has been possible by invoking values of Tm for solutions containing NaCl salt only. Resulting theoretical values of enthalpy, entropy, and heat capacity (for NaCl salt-containing solutions) and of Tm as a function of NaCl concentration in NaCl + MgCl2 solutions have thus been obtained. Qualitative and, to a large extent, quantitative reproduction of the experimental Tm, DeltaHm, DeltaSm, and DeltaCp values have been found from the results of polyelectrolyte theories. However, the quantitative resemblance of experimental data is considerably better for PB theory as compared to the CC model. Furthermore, some rather implausible qualitative conclusions are obtained within the CC results for DNA melting in NaCl + MgCl2 solutions. Our results argue in favor of the Poisson-Boltzmann theory, as compared to the counterion condensation theory.

We present a methodology to quantify the essential interactions at the interface between inorganic solid nanoparticles (NPs) and biological molecules. Our model is based on pre-calculation of the repetitive contributions to the interaction from molecular segments, which allows us to efficiently scan a multitude of molecules and rank them by their adsorption affinity. The interaction between the biomolecular fragments and the nanomaterial are evaluated using a systematic coarse-graining scheme starting from all-atom molecular dynamics simulations. The NPs are modelled using a two-layer representation, where the outer layer is parameterized at the atomistic level and the core is treated at the continuum level using Lifshitz theory of dispersion forces. We demonstrate that the scheme reproduces the experimentally observed features of the NP protein coronas. To illustrate the use of the methodology, we compute the adsorption energies for human blood plasma proteins on gold NPs of different sizes as well as the preferred orientation of the molecules upon adsorption. The computed energies can be used for predicting the composition of the NP-protein corona for the corresponding material.