Atomistic Simulation of the Ion-Assisted Deposition of Silicon Dioxide Thin Films.

A systematic study of the most significant parameters of the ion-assisted deposited silicon dioxide films is carried out using the classical molecular dynamics method. The energy of the deposited silicon and oxygen atoms corresponds to the thermal evaporation of the target; the energy of the assisting oxygen ions is 100 eV. It is found that an increase in the flow of assisting ions to approximately 10% of the flow of deposited atoms leads to an increase in density and refractive index by 0.5 g/cm3 and 0.1, respectively. A further increase in the flux of assisting ions slightly affects the film density and density profile. The concentration of point defects, which affect the optical properties of the films, and stressed structural rings with two or three silicon atoms noticeably decrease with an increase in the flux of assisting ions. The film growth rate somewhat decreases with an increase in the assisting ions flux. The dependence of the surface roughness on the assisting ions flux is investigated. The anisotropy of the deposited films, due to the difference in the directions of motion of the deposited atoms and assisting ions, is estimated using the effective medium approach.

Short-range combined water model.

The short-range combined water model (SRCW model) for the calculation of the hydration free energy of the non-polar solutes is presented. A mixed explicit/implicit representation of the solvent is used in the model. A thermodynamic basis for the boundary potential between explicit and implicit parts of the simulation area is derived. A simple functional form for the boundary potential minimizing the water density fluctuations in the explicit part is found. Hydration free energies of the model solutes are calculated in the frame of the developed model. Obtained values are in the good agreement with results of the Monte Carlo simulation using the periodic boundary conditions.

[Supercomputer investigation of the protein-ligand system low-energy minima].

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

Specific features of the dielectric continuum solvation model with a position-dependent permittivity function.

We consider a modified formulation for the recently developed new approach in the continuum solvation theory (Basilevsky, M. V.; Grigoriev, F. V.; Nikitina, E. A.; Leszczynski, J. J. Phys. Chem. B 2010, 114, 2457) which is based on the exact solution of the electrostatic Poisson equation with the space-dependent dielectric permittivity. Its present modification ensures the property curl E = 0 for the electric strength field E inherent to this solution, which is the obligatory condition imposed by Maxwell equations. The illustrative computation is made for the model system of the point dipole immersed in a spherical cavity of excluded volume.

Computation of the contribution from the cavity effect to protein-ligand binding free energy.

We present results of the investigation of the cavity creation/annihilation effect in view of formation of the protein-ligand (PL) complexes. The protein and ligand were considered as rigid structures. The change of the cavity creation/annihilation free energy DeltaG(cav) was calculated for three PL complexes using the thermodynamic integration procedure with the original algorithm for growing the interaction potential between the cavity and the water molecules. The thermodynamic cycle consists of two stages, annihilation of the cavity of the ligand for the unbound state and its creation at the active site of the protein (bound state). It was revealed that for all complexes under investigation, the values of DeltaG(cav) are negative and favorable for binding. The main contribution to DeltaG(cav) appears due to the annihilation of the cavity of the ligand. All computations were made using the parallel version of CAVE code, elaborated in our preceding work.

Cavitation free energy for organic molecules having various sizes and shapes.

Cavitation free energy DeltaG(cav), corresponding to the formation of an excluded volume cavity in water, is calculated for a large set of organic molecules employing the thermodynamic integration procedure, which is realized as the original two-step algorithm for growing the interaction potential between the hard cavity wall and the water molecules. A large variety of solute systems is considered. Their characteristic radii change in the range 3-7 A; spherical cavities with radii 3-6 A are also studied. The interaction between water molecules is described by the four-site nonpolarizable TIP4P model. The diversity of the trial molecular set is provided by using a specially formulated nonspherical criterion classifying the cavity shapes according to their deviation from a sphere. Molecular objects were partly taken from the data base NCI Diversity with the aid of this criterion. The so-computed free energies are approximated by the linear volume dependence DeltaG(cav)V = XiV, where V is the cavity volume. This relation works fairly well until the cavity size becomes very large (the effective radius larger than 7 A). The volume dependence valid for solutes of arbitrary shapes can be included in a calculation of the nonpolar free energy component as required in the implicit water model.

Computation of entropy contribution to protein-ligand binding free energy.

The entropy contribution DeltaS to protein-ligand binding free energy is studied for nine protein-lipid complexes. The entropy effect from the loss of the translational/rotational degrees of freedom (DeltaStr) is calculated using the ideal gas approach. The change in the vibrational entropy (DeltaSvib) is calculated using the effective quantum oscillator approach with frequencies derived from the coordinate covariance matrix, so the inharmonic effects are taken into account. The change in the entropy of solvation (DeltaSsolv) is considered using the binomial cell model (developed by the authors) for the hydrophobic effect. The entropy contribution from loss of conformations that are available for the free ligand (DeltaSconf) is also estimated. It is revealed that the negative in view of binding term DeltaStr is only partly compensated by increasing of DeltaSvib, so T(DeltaStr+DeltaSvib+DeltaSconf)<0 for all complexes under investigation, but taking into account DeltaSsolv leads to significantly increased DeltaS. For all complexes except biotin-streptavidin, the results are found to be in reasonable agreement with experimental data.

Excluded volume effect for large and small solutes in water.

The cavitation effect, i.e., the process of the creation of a void of excluded volume in bulk solvent (a cavity), is considered. The cavitation free energy is treated in terms of the information theory (IT) approach [Hummer, G.; Garde, S.; Garcia, A. E.; Paulaitis, M. E.; Pratt, L. R. J. Phys. Chem. B 1998, 102, 10469]. The binomial cell model suggested earlier is applied as the IT default distribution p(m) for the number m of solute (water) particles occupying a cavity of given size and shape. In the present work, this model is extended to cover the entire range of cavity size between small ordinary molecular solutes and bulky biomolecular structures. The resulting distribution consists of two binomial peaks responsible for producing the free energy contributions, which are proportional respectively to the volume and to the surface area of a cavity. The surface peak dominates in the large cavity limit, when the two peaks are well separated. The volume effects become decisive in the opposite limit of small cavities, when the two peaks reduce to a single-peak distribution as considered in our earlier work. With a proper interpolation procedure connecting these two regimes, the MC simulation results for model spherical solutes with radii increasing up to R = 10 A [Huang, D. H.; Geissler, P. L.; Chandler, D. J. Phys. Chem. B 2001, 105, 6704] are well reproduced. The large cavity limit conforms to macroscopic properties of bulk water solvent, such as surface tension, isothermal compressibility and Tolman length. The computations are extended to include nonspherical solutes (hydrocarbons C1-C6).