Forcefields Supported by the Discover Program

The CVFF (consistent valence forcefield) forcefield was parameterized to reproduce peptide and protein properties. It is a Class I forcefield having some anharmonic and cross term enhancements. As the default forcefield in the Discover program, it has been used extensively on these systems and can be considered well tested and characterized.

The CFF91 (consistent forcefield) forcefield is a second-generation, or Class II, forcefield (Maple et al. 1988, 1994, in press, Dinur and Hagler 1991, Waldman and Hagler 1993, Hill and Sauer 1994, Hwang et al. in press, Hagler and Ewig in press, Sun et al. in press). It was parameterized against a wide range of experimental observables and has been shown to be more accurate than Class I forcefields such as CVFF and AMBER. Because it is new, it has not been tested as extensively as the other two forcefields and thus is not as well characterized.

The ESFF (extensible systematic forcefield) forcefield is a new rule-based forcefield, which is currently under development. In contrast to other forcefields supported by Biosym/MSI, which target high accuracy for a limited number of functional groups, the goal of this forcefield is to provide the widest possible coverage of the periodic table. The objectives of the current efforts are twofold: to provide a usable forcefield covering organic and organometallic compounds and to provide a foundation for future compatible forcefield development. The immediate focus is to reproduce the structures of isolated molecules as well as crystals. Reasonable steps are being taken to also reproduce the shape of the potential energy surface (i.e., the vibrational frequencies), but the scope of the current effort does not extend to highly accurate vibrational frequencies or other properties such as conformational energies.

The AMBER forcefield (Weiner et al. 1984, 1986) was parameterized against a limited number of compounds related to proteins and nucleic acids. It is a quadratic diagonal Class I forcefield that has been cited frequently in the literature and may be considered well characterized. It has also been extended to polysaccharides (Homans 1990).

The ability to choose among several forcefields has several advantages:

1. A broader range of systems can be treated. The CVFF forcefield was originally created for modeling proteins and peptides and has been extended to handle more general systems having similar functional groups. The addition of the ESFF forcefield has extended the range even further. The AMBER forcefield includes parameters for DNA and RNA, as well as for their interactions with proteins. The AMBER forcefield now has parameters for carbohydrates and polysaccharides (Homans 1990). The CFF91 forcefield currently includes parameters for all functional groups appropriate for protein simulations.

2. Identical calculations with two or more independent forcefields can be compared to assess the dependence of the results on the forcefield. For example, amino acid parameters are defined in the CVFF, AMBER, and CFF91 forcefields, so peptide and protein calculations can be compared directly.

3. The new functional forms needed for the various energy expressions increase the flexibility of the Discover program and allow different energy terms to be compared. Approximations such as a distance-dependent dielectric constant or scaling of 1-4 nonbond interactions can be assessed.

4. The development of new forcefields at Biosym/MSI and elsewhere continues to provide more accurate and general forcefields. As experience is gained in parameterizing forcefields and as new experimental data become available, the range of both properties and systems fit by these newer forcefields will increase. The CFF91 forcefield is one example of a second-generation forcefields.

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