F. J. Luque

Optimization of solute cavities and van der Waals parameters in ab initio MST-SCRF calculations of neutral molecules

The cavity used to represent the solute/water interface in Miertus–Scrocco–Tomasi self‐consistent reaction field (MST‐SCRF) calculations of neutral molecules has been optimized by fitting to experimental data. The study is focused on the refinement of the van der Waals radii of polar and apolar hydrogens and of the van der Waals parameters used to compute the dispersion/repulsion contribution to the total free energy of hydration. When a scaling coefficient of 1.25 is used to build the solute cavity, comparison of 6‐31G*/MST results with experimental data demonstrates that the optimum van der Waals radii for hydrogens are around 1.2 Å (apolar) and 0.9 Å (polar). The optimization of the solute cavity and the refinement of the van der Waals parameters lead to root mean square deviations in the computed free energy of hydration of only 0.9 kcal/mol for the 23 molecules considered in this study.

Essential Dynamics: A Tool for Efficient Trajectory Compression and Management

We present a simple method for compression and management of very large molecular dynamics trajectories. The approach is based on the projection of the Cartesian snapshots collected along the trajectory into an orthogonal space defined by the eigenvectors obtained by diagonalization of the covariance matrix. The transformation is mathematically exact when the number of eigenvectors equals 3N-6 (N being the number of atoms), and in practice very accurate even when the number of eigenvectors is much smaller, permitting a dramatic reduction in the size of trajectory files. In addition, we have examined the ability of the method, when combined with interpolation, to recover dense samplings (snapshots collected at a high frequency) from more sparse (lower frequency) data as a method for further data compression. Finally, we have investigated the possibility of using the approach when extrapolating the behavior of the system to times longer than the original simulation period. Overall our results suggest that the method is an attractive alternative to current approaches for including dynamic information in static structure files such as those deposited in the Protein Data Bank.

EXTENSION OF MST/SCRF METHOD TO ORGANIC SOLVENTS : AB INITIO AND SEMIEMPIRICAL PARAMETRIZATION FOR NEUTRAL SOLUTES IN CCL4

The self‐consistent reaction field (SCRF) method proposed by Miertus, Scrocco, and Tomasi (MST) was extended to solutions of neutral solutes in CCl4. A detailed parametrization of the solute/solvent interface and of the “hardness” atomic parameters determining the van der Waals interactions was performed from comparison with experimental data and Monte Carlo simulations. The parametrization was carried out at both ab initio (6‐31G*) and semiempirical (MNDO, AM1, PM3) levels. The MST/SCRF optimized versions provide accurate estimates of the free energy of solvation in CCl4 for the series of molecules studied. Furthermore, a precise description of the solvent effect on different chemical processes in CCl4 solution supports the reliability of the parametrization.

Induced dipole moment and atomic charges based on average electrostatic potentials in aqueous solution

A Monte Carlo quantum mechanical and molecular mechanical (QM/MM) simulation method using the combined Austin model 1 (AM1) and TIP3P potential is proposed to evaluate the average molecular electrostatic potentials (MEP) in aqueous solution. It was demonstrated that the average MEP in water can provide a quantitative account of the solvent polarization effect on molecular dipole moments and atomic charges. The computed induced dipole moments from the Monte Carlo AM1/TIP3P simulation method were found to be in good agreement with those predicted by continuum self‐consistent reaction field theory using the AM1 and 6‐31G(d) wave functions. The findings also indicate that the minimal basis set adopted by the AM1 method can capture the solvent effect effectively. Finally, good correlations in the MEP‐fitted charges were obtained between different methods. These results should be useful for developing polarizable intermolecular potential functions (PIPF).

Development of optimized MST/SCRF methods for semiempirical calculations: The MNDO and PM3 Hamiltonians

The self‐consistent reaction field (SCRF) method proposed by Miertus, Scrocco, and Tomasi (MST) has been optimized for MNDO and PM3 semiempirical Hamiltonians. Different algorithms used to compute the molecular electrostatic potential (MEP) and different solute cavities have been investigated. The ability of the optimized models to reproduce experimental free energies of solvation and to mimic the solvent effect in several chemical processes has been compared with the ab initio and AM1 versions of the MST method as well as with experimental data.

Optimization of the cavity size for ab initio MST-SCRF calculations of monovalent ions

Abstract We present a study on the determination of the optimum solute cavity to be used for simulating the solute/solvent interface in ab initio self-consistent reaction field (SCRF) calculations of charged molecules. The SCRF continuum model proposed by Miertus, Scrocco and Tomasi is considered. Semiempirical and ab initio gas phase optimizations, and Monte Carlo simulations of systems in aqueous solution suggest that the first hydration shell approaches more to a charged molecule than to a neutral species. Comparison between 6–31 ++G * /MST and experimental free energies of hydration suggests that the optinum cavity for charged molecules is placed at around 1.10–1.15 times the van der Waals radii, which implies a reduction of ≈ 0.1 A with respect to the optimum cavity size for neutral molecules.

Salt bridge interactions: stability of the ionic and neutral complexes in the gas phase, in solution, and in proteins.

A theoretical study on the stability of the salt bridges in the gas phase, in solution, and in the interior of proteins is presented. The study is mainly focused on the interaction between acetate and methylguanidinium ions, which were used as model compounds for the salt bridge between Asp (Glu) and Arg. Two different solvents (water and chloroform) were used to analyze the effect of varying the dielectric constant of the surrounding media on the salt bridge interaction. Calculations in protein environments were performed by using a set of selected protein crystal structures. In all cases attention was paid to the difference in stability between the ion pair and neutral hydrogen‐bonded forms. Comparison of the results determined in the gas phase and in solution allows us to stress the large influence of the environment on the binding process, as well as on the relative stability between the ionic and neutral complexes. The high anisotropy of proteins and the local microenvironment in the interior of proteins make a decisive contribution in modulating the energetics of the salt bridge. In general, the formation of salt bridges in proteins is not particularly favored, with the ion pair structure being preferred over the interaction between neutral species. Proteins 32:67–79, 1998.

An optimized AM1/MST method for the MST-SCRF representation of solvated systems

The AM1/MST strategy for the computation of hydrated neutral molecules has been optimized. For this purpose, we have systematically explored the best cavity definition, the most suitable strategy to compute the molecular electrostatic potential (MEP), and the use of MEP scaling factors to correct the semiempirical MEPs. As a result, we have developed an optimized version of the AM1/MST method, which allows us to reproduce well the experimental free energies of hydration (root mean square, rms, deviation in the range of 1 kcal/mol) as well as the water‐induced dipoles computed at the 6‐31G*/MST level (rms deviations in the range of 0.3 D).

Suitability of the PM3-derived molecular electrostatic potentials

A systematic study of the suitability of PM3‐derived molecular electrostatic potentials (MEPs) is presented. Forty‐six MEP minima, 81 electrostatic charges, and 17 electrostatic dipoles were determined at the PM3 level and compared with those obtained from the ab initio 6‐31G* wave function, as well as from the semiempirical MNDO and AM1 wave functions. The statistical results of the comparison analysis between semiempirical and ab initio 6‐31G* MEPs show that PM3 is in general reliable for the study of the MEP minima but a mediocre method as a source of electrostatic charges.

A new strategy for the representation of environment effects in semi-empirical calculations based on Dewar's Hamiltonians

Abstract A strategy for the computation of the properties of chemical systems in condensed media is presented. This strategy consists of the implementation of Tomasis continuum model within the framework of Dewars semi-empirical methods. Sample calculations evidence the ability of this strategy to predict not only thermodynamic quantities but also the influence of the environment on solute properties. The characteristics of this methodology make it a promising tool for the study of large biochemical systems.