Molecular modeling free energy

Rozanska, X. Chipot, C., Modeling ion-ion interaction in proteins a molecular dynamics free energy calculation of the guanidinium-acetate association, J. Chem. Phys. 2000, 112, 9691-9694. 

Molecular dynamics free-energy perturbation simulations utilizing the empirical valence bond model have been used to study the catalytic action of -cyclodextrin in ester hydrolysis. Reaction routes for nucleophilic attack on m-f-butylphenyl acetate (225) by the secondary alkoxide ions 0(2) and 0(3) of cyclodextrin giving the R and S stereoisomers of ester tetrahedral intermediate were examined. Only the reaction path leading to the S isomer at 0(2) shows an activation barrier that is lower (by about 3kcal mol ) than the barrier for the corresponding reference reaction in water. The calculated rate acceleration was in excellent agreement with experimental data. ... 

As tlie upper leg is a gas-phase quantity, it can be computed taking advantage of all of the technology discussed in earlier chapters. The two vertical legs, on the other hand, consist exclusively of free energies of solvation. Thus, the development of models to efficiently compute molecular solvation free energies has been a high priority. 

The total surface energy generally is larger than the surface free energy. It is frequently the more informative of the two quantities, or at least it is more easily related to molecular models. 

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

In this chapter we shall consider four important problems in molecular n iudelling. First, v discuss the problem of calculating free energies. We then consider continuum solve models, which enable the effects of the solvent to be incorporated into a calculation witho requiring the solvent molecules to be represented explicitly. Third, we shall consider the simi lation of chemical reactions, including the important technique of ab initio molecular dynamic Finally, we consider how to study the nature of defects in solid-state materials. 

Cramer C j and D G Truhlar 1992. AM1-SM2 and PM3-SM3 Parametrized SCF Solvation Models for Free Energies in Aqueous Solution. Journal of Computer-Aided Molecular Design 6 629-666. 

Mesoscale simulations model a material as a collection of units, called beads. Each bead might represent a substructure, molecule, monomer, micelle, micro-crystalline domain, solid particle, or an arbitrary region of a fluid. Multiple beads might be connected, typically by a harmonic potential, in order to model a polymer. A simulation is then conducted in which there is an interaction potential between beads and sometimes dynamical equations of motion. This is very hard to do with extremely large molecular dynamics calculations because they would have to be very accurate to correctly reflect the small free energy differences between microstates. There are algorithms for determining an appropriate bead size from molecular dynamics and Monte Carlo simulations. 

There are two ways in which the volume occupied by a sample can influence the Gibbs free energy of the system. One of these involves the average distance of separation between the molecules and therefore influences G through the energetics of molecular interactions. The second volume effect on G arises from the contribution of free-volume considerations. In Chap. 2 we described the molecular texture of the liquid state in terms of a model which allowed for vacancies or holes. The number and size of the holes influence G through entropy considerations. Each of these volume effects varies differently with changing temperature and each behaves differently on opposite sides of Tg. We shall call free volume that volume which makes the second type of contribution to G. 

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