Hierarchical pattern of microfibrils in a 3D fluorapatite-gelatine nanocomposite: simulation of a bio-related structure building process.

The shape development of a biomimetic fluorapatite-gelatine nanocomposite on the mum scale is characterised by a fractal mechanism with the origin being intrinsically coded in a (central) elongated hexagonal-prismatic seed. The 3D superstructure of the seed is distinctively overlaid by a pattern consisting of gelatine microfibrils. The orientation of the microfibrils is assumed to be controlled by an intrinsic electrical field generated by the nanocomposite during development and growth of the seed.

Molecular visualization in the rational drug design process.

The visualization of molecular scenarios on an atomic level can help to interpret experimental and theoretical findings. This is demonstrated in this review article with the specific field of drug design. State-of-the-art visualization techniques are described and applied to the different stages of the rational design process.

Parameterization of an empirical model for the prediction of n-octanol, alkane and cyclohexane/water as well as brain/blood partition coefficients.

Quantitative information of solvation and transfer free energies is often needed for the understanding of many physicochemical processes, e.g the molecular recognition phenomena, the transport and diffusion processes through biological membranes and the tertiary structure of proteins. Recently, a concept for the localization and quantification of hydrophobicity has been introduced (Jäger et al.

Hybrid integral equation/simulation model for enhancing free energy computations.

Integral equation theory is used for extrapolating free energy data from molecular simulations of a reference state with respect to a modification of the interaction potential. The methodology is applied to the correction of artefacts arising from potential shifting and truncation. Corrective contributions for the hydration free energy with respect to the full potential are analysed for the case that both the solute-solvent as well as the solvent-solvent potentials are truncated and modified by a shifted-force term, reaching beyond the range of the dielectric continuum approximation and simple long-range correction expressions.

An atomistic simulation scheme for modeling crystal formation from solution.

We present an atomistic simulation scheme for investigating crystal growth from solution. Molecular-dynamics simulation studies of such processes typically suffer from considerable limitations concerning both system size and simulation times. In our method this time-length scale problem is circumvented by an iterative scheme which combines a Monte Carlo-type approach for the identification of ion adsorption sites and, after each growth step, structural optimization of the ion cluster and the solvent by means of molecular-dynamics simulation runs.

Determination of the interfacial water content in protein-protein complexes from free energy simulations.

The question as to how many tightly or weakly bound water molecules are located in interfaces between protein-protein complex constituents is addressed from a phase equilibrium point of view by developing a theory in the canonical ensemble. A fast method based on free energy simulations is described for computing the number of water molecules in the interface regions. Results are given for 211 interfacial cavities of 26 antigen-antibody complexes for which experimentally determined structures are found in the Protein Data Bank.

Pattern recognition strategies for molecular surfaces: III. Binding site prediction with a neural network.

An algorithm for the identification of possible binding sites of biomolecules, which are represented as regions of the molecular surface, is introduced. The algorithm is based on the segmentation of the molecular surface into overlapping patches as described in the first article of this series.1 The properties of these patches (calculated on the basis of physical and chemical properties) are used for the analysis of the molecular surfaces of 7821 proteins and protein complexes.

Parametrization strategy for the MolFESD concept: quantitative surface representation of local hydrophobicity.

We derive a new model for the established concept of the molecular free energy surface density (MolFESD) yielding a more rigorous representation of local surface contributions to the overall hydrophobicity of a molecule. The model parametrization makes efficient use of both local and global information about solvation thermodynamics, as formulated earlier for the problem of predicting free energies of hydration. The free energy of transfer is separated into an interaction contribution and a term related to the cavity formation.

Molecular dynamics studies on the aggregation of Y-shaped fluoroalkanes.

Molecular dynamics (MD) calculations have been performed on the aggregation of clusters with up to 128 Y-shaped perfluoroalkylated molecules of the type C10F20[C7H15]2 (Y-A/128) and C10H20[C7F15]2 (Y-B/128) as well as mixed clusters (Y-A/64+Y-B/64) using the AMBER 5 program. The effect of the segregation tendency of the chemically different parts and the influence of the steric repulsion due to the wedge shape of the molecules on the structure formation have been studied. The results have been analyzed by snapshots, radial atom pair distribution functions, orientational correlation functions as well as diffusion coefficients and are compared with the corresponding findings on clusters of alkanes and perfluoroalkanes.

Pattern recognition strategies for molecular surfaces. II. Surface complementarity.

Fuzzy logic based algorithms for the quantitative treatment of complementarity of molecular surfaces are presented. Therein, the overlapping surface patches defined in article I1 of this series are used. The identification of complementary surface patches can be considered as a first step for the solution of molecular docking problems.

Pattern recognition strategies for molecular surfaces. I. Pattern generation using fuzzy set theory.

A new method for the characterization of molecules based on the model approach of molecular surfaces is presented. We use the topographical properties of the surface as well as the electrostatic potential, the local lipophilicity/hydrophilicity, and the hydrogen bond density on the surface for characterization. The definition and the calculation method for these properties are reviewed shortly.