Effective fragment potentials

In this contribution, we describe work from our group in the development and application of alternatives that allow the explicit inclusion of environment effects while treating the most relevant part of the system with full quantum mechanics. The first methodology, dubbed MD/QM, was used for the study of the electronic spectrum of prephenate dianion in solution [18] and later coupled to the Effective Fragment Potential (EFP) [19] to the study of the Claisen rearrangement reaction from chorismate to prephenate catalyzed by the chorismate mutase (CM) enzyme [20]. 

Another method that has been applied by our group to the study of enzymatic reactions is the Effective Fragment Potential (EFP) method [19]. The EFP method (developed at Mark Gordon s group at Iowa State University) allows the explicit inclusion of environment effects in quantum chemical calculations. The solvent, which may consist of discrete solvent molecules, protein fragments or other material, is treated explicitly using a model potential that incorporates electrostatics, polarization, and exchange repulsion effects. The solute, which can include some... 

This chapter reviewed some of our group s contributions to the development and application of QM/MM methods specifically as applied to enzymatic reactions, including the use of sequential MD/QM methods, the use of effective fragment potentials for reaction mechanisms, the development of the new QM/MM interface in Amber, as well as the implementation and optimization of the SCC-DFTB method in the Amber program. This last implementation allows the application of advanced MD and sampling techniques available in Amber to QM/MM problems, as exemplified by the potential and free energy surface surfaces for the reaction catalyzed by the Tripanosoma cruzi enzyme /ram-sialidasc shown here. 

COARSE-GRAINED INTERMOLECULAR POTENTIALS DERIVED FROM THE EFFECTIVE FRAGMENT POTENTIAL APPLICATION TO WATER, BENZENE, AND CARBON TETRACHLORIDE... 

Keywords Coarse-graining, Force-matching, Effective fragment potential method, Molecular... 

Chorismate mutase catalyzes the Claisen rearrangement of chorismate to prephenate at a rate 106 times greater than that in solution (Fig. 5.5). This enzyme reaction has attracted the attention of computational (bio)chemists, because it is a rare example of an enzyme-catalyzed pericyclic reaction. Several research groups have studied the mechanism of this enzyme by use of QM/MM methods [76-78], It has also been studied with the effective fragment potential (EFP) method [79, 80]. In this method the chemically active part of an enzyme is treated by use of the ab initio QM method and the rest of the system (protein environment) by effective fragment potentials. These potentials account... 

In addition to these external electric or magnetic field as a perturbation parameter, solvents can be another option. Solvents having different dielectric constants would mimic different field strengths. In the recent past, several solvent models have been used to understand the reactivity of chemical species [55,56]. The well-acclaimed review article on solvent effects can be exploited in this regard [57]. Different solvent models such as conductor-like screening model (COSMO), polarizable continuum model (PCM), effective fragment potential (EFP) model with mostly water as a solvent have been used in the above studies. 

M.S. Gordon, M.A. Freitag, P. Bandyopadhyay, J.H. Jensen, V. Kairys, W.J. Stevens, The effective fragment potential method A QM-based MM approach to modeling environmental effects in chemistry, J. Phys. Chem. A105 (2001) 293. 

S. Yoo, F. Zahariev, S. Sok, M.S. Gordon, Solvent effects on optical properties of molecules A combined time-dependent density functional theory/effective fragment potential approach, J. Chem. Phys. 129 (2008) 144112. 

In general, for each acid HA, the HA-(H20) -Wm model reaction system (MRS) comprises a HA (H20) core reaction system (CRS), described quantum chemically, embedded in a cluster of Wm classical, polarizable waters of fixed internal structure (effective fragment potentials, EFPs) [27]. The CRS is treated at the Hartree-Fock (HF) level of theory, with the SBK [28] effective core potential basis set complemented by appropriate polarization and diffused functions. The W-waters not only provide solvation at a low computational cost they also prevent the unwanted collapse of the CRS towards structures typical of small gas phase clusters by enforcing natural constraints representative of the H-bonded network of a surface environment. In particular, the structure of the Wm cluster equilibrates to the CRS structure along the whole reaction path, without any constraints on its shape other than those resulting from the fixed internal structure of the W-waters. 

Methanol-water mixtures were studied by Adamovic and Gordon who used the so called effective-fragment-potential method, an approach of the type discussed in section IID, for finite (Me0H/H20) clusters with n = 2,3,. .., 8. Some of their findings were tested by using accurate, parameter-free, electronic-structure methods. The main outcome is the organization of the H2O and MeOH molecules relative to each other, which then is expected to be representative for macroscopic mixtures of water and methanol. 

Inclusion of dispersion effect in the MP2 based effective fragment potential method (EFP1).132... 

The effective fragment potential (EFP) is a more recent scheme that goes beyond interaction modeling. It incorporates electrical response and is targeted... 

The recent effective fragment potential (EFP) scheme [153,154] mentioned earlier is clearly a successful connection between quantum and non-quanmm mechanically described regions. The effective potentials used to represent the non-quanmm mechanical spectator molecules in the ab initio treatment (quantum region) include Coulomb interactions, polarization, and exchange repulsion. 

Ohta K, Yoshioka Y, Morokuma K, Kitaura K (1983) The effective fragment potential method an approximate ab initio MO method for large molecules. Chem Phys Lett 101 12-17... 

To address the problem of finite system size, the EFP method has also been combined with continuum models in order to model the effects of the neglected bulk solvent [125], The Onsager equation was used to obtain the dipole polarization of the solute molecule (modeled quantum mechanically) and explicit water molecules (modeled by effective fragment potentials) due to the dielectric continuum. Thus the energy becomes... 

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