[gmx-users] Forcefields and water models for protein simulations.
quantrum75 at yahoo.com
Thu Jul 16 21:01:19 CEST 2009
I recently asked a question about comparing the forcefields for protein simulations and the appropriate water model to use for the same to which Justin answered back. Thanks for the answer justin.
In addition, I found a couple of references which I think are really good for the above topics which I would like to share with other newbies (like me) as a future reference. This might be a good starting point for other to follow. They are:
For the forcefields:
1: Methods Mol Biol. 2008;443:63-88.
Comparison of protein force fields for molecular dynamics simulations.
Guvench O, MacKerell AD Jr.
Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD, USA.
In the context of molecular dynamics simulations of proteins, the term "force field" refers to the combination of a mathematical formula and associated parameters that are used to describe the energy of the protein as a function of its atomic coordinates. In this review, we describe the functional forms and parameterization protocols of the widely used biomolecular force fields Amber, CHARMM, GROMOS, and OPLS-AA. We also summarize the ability of various readily available noncommercial molecular dynamics packages to perform simulations using these force fields, as well as to use modern methods for the generation of constant-temperature, constant-pressure ensembles and to treat long-range interactions. Finally, we finish with a discussion of the ability of these force fields to support the modeling of proteins in conjunction with nucleic acids, lipids, carbohydrates, and/or small molecules.
For the water models.
2: 1: J Chem Phys. 2005 Apr 1;122(13):134508.
Solvation free energies of amino acid side chain analogs for common molecular mechanics water models.
Shirts MR, Pande VS.
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.
Quantitative free energy computation involves both using a model that is sufficiently faithful to the experimental system under study (accuracy) and establishing statistically meaningful measures of the uncertainties resulting from finite sampling (precision). In order to examine the accuracy of a range of common water models used for protein simulation for their solute/solvent properties, we calculate the free energy of hydration of 15 amino acid side chain analogs derived from the OPLS-AA parameter set with the TIP3P, TIP4P, SPC, SPC/E, TIP3P-MOD, and TIP4P-Ew water models. We achieve a high degree of statistical precision in our simulations, obtaining uncertainties for the free energy of hydration of 0.02-0.06 kcal/mol, equivalent to that obtained in experimental hydration free energy measurements of the same molecules. We find that TIP3P-MOD, a model designed to give improved free energy of hydration for methane, gives uniformly the closest match to
experiment; we also find that the ability to accurately model pure water properties does not necessarily predict ability to predict solute/solvent behavior. We also evaluate the free energies of a number of novel modifications of TIP3P designed as a proof of concept that it is possible to obtain much better solute/solvent free energetic behavior without substantially negatively affecting pure water properties. We decrease the average error to zero while reducing the root mean square error below that of any of the published water models, with measured liquid water properties remaining almost constant with respect to our perturbations. This demonstrates there is still both room for improvement within current fixed-charge biomolecular force fields and significant parameter flexibility to make these improvements. Recent research in computational efficiency of free energy methods allows us to perform simulations on a local cluster that previously required
large scale distributed computing, performing four times as much computational work in approximately a tenth of the computer time as a similar study a year ago.
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