Implicit solvent treatment

Figure 3 Schematic representation of a mixed explicit-implicit solvent treatment. A small number of water molecules are included explicitly in the vicinity of the solute while the influence of the remaining bulk is taken into account implicitly.

Fand W,(f) in turn are related through the fluctuation-dissipation theorem, v, is the particle velocity. The hydrodynamic interaction between particles associated with motion of the intervening solvent may also be included, but doing so compromises considerably the computational benefits of the implicit solvent treatment, and has not been considered in the study of polymer crystallization to date. As with the use of the thermostat in MD, the solvent is presumed small enough... 

A statistical mechanical fonnulation of implicit solvent representations provides a robust theoretical framework for understanding the influence of solvation biomolecular systems. A decomposition of the free energy in tenns of nonpolar and electrostatic contributions, AVF = AVF " + AVF ° , is central to many approximate treatments. An attractive and widely used treatment consists in representing the nonpolar contribution AVF " by a SASA surface tension term with Eq. (15) and the electrostatic contribution by using the... 

It is possible to go beyond the SASA/PB approximation and develop better approximations to current implicit solvent representations with sophisticated statistical mechanical models based on distribution functions or integral equations (see Section V.A). An alternative intermediate approach consists in including a small number of explicit solvent molecules near the solute while the influence of the remain bulk solvent molecules is taken into account implicitly (see Section V.B). On the other hand, in some cases it is necessary to use a treatment that is markedly simpler than SASA/PB to carry out extensive conformational searches. In such situations, it possible to use empirical models that describe the entire solvation free energy on the basis of the SASA (see Section V.C). An even simpler class of approximations consists in using infonnation-based potentials constructed to mimic and reproduce the statistical trends observed in macromolecular structures (see Section V.D). Although the microscopic basis of these approximations is not yet formally linked to a statistical mechanical formulation of implicit solvent, full SASA models and empirical information-based potentials may be very effective for particular problems. 

Im W, Chen J, Brooks CL III (2006) Peptide and protein folding and conformational equilibria Theoretical treatment of electrostatics and hydrogen bonding with implicit solvent models. Adv Protein Chem 72 173-198. 

The weakest point of our approach is the treatment of the bulk solvent. The energies derived from an implicit solvent model like IPCM are mainly based on energy calculations on gas-phase structures and effects of explicit solvent molecules are not included. 

Although many satisfactory VCD studies based on the gas phase simulations have been reported, it may be necessary to account for solvent effects in order to achieve conclusive AC assignments. Currently, there are two approaches to take solvent effects into account. One of them is the implicit solvent model, which treats a solvent as a continuum dielectric environment and does not consider the explicit intermolecular interactions between chiral solute and solvent molecules. The two most used computational methods for the implicit solvent model are the polarizable continuum model (PCM) [93-95] and the conductor-like screening model (COSMO) [96, 97]. In this treatment, geometry optimizations and harmonic frequency calculations are repeated with the inclusion of PCM or COSMO for all the conformers found. Changes in the conformational structures, the relative energies of conformers, and the harmonic frequencies, as well as in the VA and VCD intensities have been reported with the inclusion of the implicit solvent model. The second approach is called the explicit solvent model, which takes the explicit intermolecular interactions into account. The applications of these two approaches, in particular the latter one will be further discussed in Sect. 4.2. 

For macromolecules in solution, treatment of conformational fluctuations and shape variations, which might be treated by implicit solvent models, is the most important issue for simulations with periodic boundary conditions. The present... 

However, the field is far from being established, and further developments are required, especially in order to extend the time-independent treatment to large macromolecular systems in the condensed phase or to allow for reliable studies in case some part of the vibrational problem is related to highly anharmonic PESs involving large-amplitude motions or solvent librations. There, use of effective QM/ MM schemes combined with implicit solvent methods would probably represent a viable choice to reduce the computational cost of otherwise prohibitively expensive anharmonic frequency analysis. Another field where the potentialities of time-independent approaches have not yet been fully assessed is that of ultrafast vibrational spectroscopies, whose interest has enormously increased in the last years, due to their... 

In the simulation of molecules in aqueous solution, treatment of the solvent and solvent ions is particularly demanding both theoretically and computationally. Continuum or implicit solvent models provide a computationally efficient alternative to the inclusion of explicit solvent molecules. These models typically treat electrostatic and nonpolar contributions separately. A popular approach is to treat, respectively, the former with a continuum electrostatics model and the latter with a surface area model. These models often provide free energies and enthalpies to an accuracy that is comparable to, or better than, that of explicit solvent models, but with two or more orders of magnitude less computation. Other properties such as solvent induced forces, solvent structural features and specific hydrogen-bonding interactions are better treated with explicit solvent models... 

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