Validation of Force Fields

The quality of a force field calculation depends on two things how appropriate is the mathematical form of the energy expression, and how accurate are the parameters. If elaborate forms for the individual interaction terms have been chosen, and a large 

Validation of a force field is typically done by showing how accurately it reproduces reference data, which may or may not have been used in the actual parameterization. Since different force fields employ different sets of reference data, it is difficult to compare their accuracy directly. Indeed there is no single best force field, each has its advantages and disadvantages. They pert orm best for the type of compounds used in the parameterization, but may give questionable results for other systems. Table 2.6 gives some typical accuracies for AH that can be obtained with the MM2 force field. 

The average error is the difference between the calculated and experimental AHf. In this connection it should be noted that the average error in the experimental data for the hydrocarbons is U.40kcal/mol, i.e. MM2 essentially reproduces the expeiimeiiLs to within the experimental uncertainty. 

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Experimental structures are often the basis for computational studies they are used as input structures for structure optimizations and conformational searches, for the parameterization and validation of force fields and for analyzing the effects of crystal lattices. More than 200,000 experimental structures have been reported, and the majority are found in the Cambridge Structural Data Base (CSD, small molecular structures which include carbon atoms) the Inorganic Crystals Structure Database (ICSD) and the Protein Data Base (PDB this database includes X-ray as well as optimized structures based on NMR data). 

Validation of Force Fields Table 2.6 Average errors in heat of formations ... 

In the last several years, improved alchemical methodologies and increased computer power have made it possible to compute the free energies of large sets of small molecules wifh precision of less than 0.1 kcal/mol, sufficient to verify the validity of force-field parameters for small molecules [38,64,104-110]. Similar gains in efficiency were obtained for small molecule solvation through variations on Monte Carlo sampling of the Gibbs ensemble [111-114]. 

It is our strong belief that in the next years theory will not only serve as a post-experiment interpretation tool or a simple "black box" able to predict experimental quantities (even though these already represent highly complex duties), but it will provide a sophisticated tool able to obtain complementary information with respect to experimental quantities and to see many things that are precluded to experiments. In order to do so theory must rely on a well established approximation to the true forces governing the nuclear motion. In this sense, the validation of force fields is crucial. 

Fig. 26.2 Computational scheme followed in the derivation and validation of force field...

A comparison of force fields as derived and used by different authors is therefore possible only to a limited extent. Any meaningful comparison has to be performed by calculating a large set of molecular properties which comprises the ranges of validity of all force fields under comparison. By experience, calculated structural parameters are generally less sensitive to changes of potential constants than energetical and vibrational quantities. 

The answer to the first question is obvious, if not necessarily trivial one should pick the force field that has previously been shown to be most effective for the most closely related problem one can find. That demonstration of effectiveness may have taken place within the process of parameterization (i.e., if one is interested in conformational properties of proteins, one is more likely to be successful with a force field specifically parameterized to model proteins than with one which has not been) or by post-development validation. Periodically in the literature, papers appear comparing a wide variety of force fields for some well-defined problem, and the results can be quite useful in guiding the choices of subsequent... 

The CLAP model has permitted access to the molecular properties of ionic liquids through molecular simulation experiments. Before these results could be fully explored, it was necessary to validate the force field parameters by comparing experimental results to the in silico measurements. Ionic liquids have a nonmeasurable vapor pressure at room temperature conditions or indeed for the larger part of their liquid temperature range. This means that the traditional way to validate a molecular... 

Unfortunately, experimental data may be non-existent or difficult to obtain for particular classes of molecules. Quantum mechanics calculations are thus increasingly used to provide the data for the parametrisatlon of molecular mechanics force fields. This is an important development because it greatly extends the range of chemical systems that can be treated using the force-field approach. Ab initio calculations are able to reproduce experimental results for small representative systems. Clearly, one should be careful to properly validate a force field derived in such a way by testing against experimental data if at all possible. 

Validation of the Applicability of Force Fields to Reproduce Ab Initio Noncovalent Interactions Involving Aromatic Groups... 

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