Parameterization force field methods

Theoretical models include those based on classical (Newtonian) mechanical methods—force field methods known as molecular mechanical methods. These include MM2, MM3, Amber, Sybyl, UFF, and others described in the following paragraphs. These methods are based on Hook s law describing the parabolic potential for the stretching of a chemical bond, van der Waal s interactions, electrostatics, and other forces described more fully below. The combination assembled into the force field is parameterized based on fitting to experimental data. One can treat 1500-2500 atom systems by molecular mechanical methods. Only this method is treated in detail in this text. Other theoretical models are based on quantum mechanical methods. These include ... 

Allen and Bevan (80) have applied the SMD technique to the study of reversible inhibitors of monoamine oxidase B, and this paper will be used as an example for discussion of the constant velocity SMD pulling method. They used the Gromacs suite of biomolecular simulation programs (18) with the united-atom Gromos 43al force field to parameterize the lipid bilayer, protein, and small-molecule inhibitors. The protein was inserted into their mixed bilayer composed of phosphatidyl choline (POPC) and phosphatidyl ethanolamine (POPE) lipids in a ratio known to be consistent for a mitochondrial membrane. Each inhibitor-bound system studied was preequilibrated in a periodic box of SPC water (20) with the simulations run using the NPT ensemble at 300 K and 1 atm pressure for 20 ns. Full atomic coordinates and velocities were saved in 200-ps increments giving five replicates for each inhibitor-bound system. A dummy atom was attached to an atom (the SMD atom shown in Fig. 7) of the inhibitor nearest to the... 

FORCE FIELD METHODS 2.3 FORCE FIELD PARAMETERIZATION 37... 

The effect of induced dipoles in the medium adds an extra term to the molecular Hamilton operator. = -r R (16.49) where r is the dipole moment operator (i.e. the position vector). R is proportional to the molecular dipole moment, with the proportional constant depending on the radius of the originally implemented for semi-empirical methods, but has recently also been used in connection with ab initio methods." Two other widely available method, the AMl-SMx and PM3-SMX models have atomic parameters for fitting the cavity/dispersion energy (eq. (16.43)), and are specifically parameterized in connection with AMI and PM3 (Section 3.10.2). The generalized Bom model has also been used in connection with force field methods in the Generalized Bom/Surface Area (GB/SA) model. In this case the Coulomb interactions between the partial charges (eq. (2.19)) are combined... 

It is beyond the scope of this short review to list every available molecular mechanics program. Only a selected few programs are mentioned here, without descriptive details of the potential functions, minimization algorithms, or comparative evaluations. Both the CHARMM and AMBER force fields use harmonic potential functions to calculate protein structures. They were developed in the laboratories of Karplus and Kollman, respectively, and work remarkably well. The CFF and force fields use more complex potential functions. Both force fields were developed in commercial settings and based extensively or exclusively on results obtained from quantum mechanics. Unlike the other molecular mechanics methods, the OPLS force field was parameterized by Jorgensen to simulate solution phase phenomena. 

Kim and Hayden and Makowska-Janusik, et al., both employ classical molecular dynamics to model the behavior of the chromophores under the application of an electric field. Although the method is classical, the force-fields are parameterized using data from both empirical data sets and ab-initio calculations. 

Many systems of interest are too large to be tackled using ab initio methods and here force field methods can be useful. Force field methods do not explicitly include the electrons, rather the energy of a system is a function only of the nuclear coordinates. The main application of molecular mechanics modelling is in the area of big systems (thousands of atoms are not uncommon). The calculations can be performed in a fraction of the computer time that would be required for an ab initio calculation. Their accuracy is determined by the quality of the parameterization of the force field. 

The EFP method attempts to overcome this parameterization problem by including electrostatics and polarization from first principles. This represents a considerable departure from the traditional MM potentials used in biomolecular simulations. The electrostatic energy remains an approximation, however, as the multipole expansions in Ueie are left uncorrected for the effects of charge penetration (C/pen). This penetration energy, Upen, is then implicit in Urep. Thus a limitation that is characteristic of all force-field methods, from the crudest MM to the most sophisticated QM/MM, is a certain lack of generality, i.e., there are arbitrary parameters that have to be refined and fitted for a particular application. 

Because of the large computational requirements of modeling macro-molecular systems, empirical force field methods are typically relied on in CADD projects. Given adequate parameterization, such calculations can offer a reasonable balance between accuracy and speed. ... 

In force field methods, for example, the interactions are parameterized as stretch, bend, torsional, van der Waals, etc., interactions. 

---