United-atom protein force fields

Force fields for biological macromolecules fall into two classes united-atom, and all-atom force fields. All-atom force fields, as the name suggests, represent all atoms in a protein explicitly. United-atom force fields, on the other hand, treat only heavy (non-hydrogen) atoms and polar hydrogen atoms explicitly, while nonpolar hydrogen atoms are not represented explicitly, but rather represented as part of the carbon atom to which they are bonded (which will have an enlarged van der Waals radius (Lennard-Jones collision diameter)). 

Examples of united-atom protein force-fields for proteins are GROMOS87 and 96,21,48 CHARMM PARAM19,49 OPLS/UA (united atom)50 and the original force fields developed for the AMBER program.51 United atom force fields were developed to reduce the computer time required for molecular dynamics simulations by reducing the number of atoms. They are still... 

As computational power advanced and became more accessible, so did the detail incorporated into the protein models. By 1977, work had moved toward united atom representations of proteins and the use of molecular mechanics to characterize the native state dynamics of BPTI in vacuo with no water included except for four crystalline waters.The empirical energy function used in this first protein MD simulation forms the basis of today s protein force fields. 

The OPLS force field is described in twtt papers, one discussing parameters for proteins W. L. Jorgensen and J. Tirado-Rives,/. Amer. (. hem. Soc., 110, 1557 (iy8K) and on e discii ssin g param eters for n iicleotide bases [J. Pranata, S. Wiersch ke, and W. L. Jorgen sen. , /.. Amer. Chem. Soc.. 117, 281(1 ( 1991)1. The force field uses the united atom concept ftir many, but not all. hydrttgens attached to carbons to allow faster calculation s on macromolecular systems. The amino and nucleic acid residue templates in HyperChein automatically switch to a united atom representation where appropriate when th e OPLS option is selected. 

This force field was developed primarily for protein and nucleic acid applications. It is a united atom force field, and there are many versions. Once again, you might like to see the Abstract of the original Paper. 

The molecular dynamics unit provides a good example with which to outline the basic approach. One of the most powerful applications of modem computational methods arises from their usefulness in visualizing dynamic molecular processes. Small molecules, solutions, and, more importantly, macromolecules are not static entities. A protein crystal structure or a model of a DNA helix actually provides relatively little information and insight into function as function is an intrinsically dynamic property. In this unit students are led through the basics of a molecular dynamics calculation, the implementation of methods integrating Newton s equations, the visualization of atomic motion controlled by potential energy functions or molecular force fields and onto the modeling and visualization of more complex systems. 

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... 

Kini RM, Evans HJ (1992) Comparison of protein models minimized by the all-atom and united atom models in the amber force field, J Biomol Structure and Dynamics, 10 265-279... 

Within the context of the above, let us try to formulate some necessary requirements for the design of a moderate resolution reduced model (based on united-atom representation and knowledge-based potentials) of real proteins and its force field ... 

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