Protein force fields condensed-phase

Duan, Y., Wu, C., Chowdhury, S., Lee, M.C., Xiong, G., Zhang, W., Yang, R., Cieplak, P., Luo, R., Lee, T., Caldwell, J., Wang, J., Kollman, P. A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem. 2003, 24, 1999-2012. 

Duan Y, Wu C, Chowdhury S et al (2003) A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J Comput Chem 24(16)4999-2012... 

Empirical or molecular mechanics (MM) potentials or force fields are traditionally the ones used for MC and MD simulations of large condensed phase systems, such as liquids or proteins. A typical force field is a sum of... 

Since only a small number of solvents are widely used in organic chemistry and there are only 20 common amino adds in proteins, well-tested empirical potential funaions may be developed and utilized to represent polypeptides and the usual solvents. Indeed, Jorgensen and co-workers have created a series of optimized potentials for liquid simulations (OPLS) for organic solvents and water, and a number of excellent force fields are available for protein simulations.26-30 Thus, it appears to be natural to divide a condensed phase system into quantum mechanical and classical regions according to the priority of interest or of importance. 

The GROMOS force field is basically meant to be used for biomolecular systems (proteins, DNA, RNA, oligosaccharides, lipids, etc.) in the condensed phase. The A-version (43A1) is the basic force field designed for molecules in solution or in crystalline form. The B-version (43B1) has been derived from the A-version in order to be used for simulating molecules in... 

The ENCAD (energy calculations and dynamics) force field has been developed by Levitt et al. for the molecular dynamics simulations of proteins and nucleic acids in solution. It employs all-atom force field parameters. For condensed phase simulations the new three-center, flexible water model has been developed. The stress has been laid on the energy conservation effect during molecular dynamics simulations without coupling simulated systems to the thermal bath. The following expression has been used to calculate potential energy of the molecular systems ... 

The focus in development of the OPLS-UA model was on the non-bonded parameters, which historically had been the most problematic, and the new approach was to perform large numbers of Monte Carlo statistical mechanics simulations of pure liquids for their refinement. This advance was made possible by increases in computer resources and the development of flexible, efficient software, namely, the BOSS program and its predecessors, that allowed rapid setup of simulations for new systems. The key point was that a principal application of such force fields was in condensed-phase simulations including protein dynamics, and testing of the force fields on prediction of well-characterized condensed-phase properties was needed. Minimally, reproduction of liquid densities and heats of vaporization provides some confidence in both the size of the molecules and the strengths of their intermolecular interactions. Furthermore, these quantities are obtained from both experiment and simulation with high precision. 

Diversity of protein structure and function is enhanced by the different chemical functional groups seen in the 20 common amino acids. This variety, however, complicates the development of empirical force field parameters for proteins. For simplicity we will simply list a number of the model compounds used for the different amino acids. This is presented in Table 1. The selection of appropriate model compounds is based on a balance between the size of the compound and the available target data. For example, a large number of gas and condensed phase data are available for methanol however, sole use of that compound for the sidechains of serine or threonine avoids accurate tests of parameters associated with the covalent connection of the sidechain to the backbone. This is overcome by the use of larger compounds such as ethanol and isopropanol. Increases in computational resources will allow for ab initio calculations on larger model compounds. However, as discussed in the previous section, care... 

---