A comparison and chemometric analysis of several molecular mechanics force fields and parameter sets applied to carbohydrates

Carbohydrates are thought to be especially difficult to model because of their highly polar functionality, their flexibility, and their differences in electronic arrangements that occur during conformational and configurational changes, such as the anomeric, exo-anomeric and gauche effects. These issues have been addressed in recent years, yielding several contributions to set up some relevant parameterizations that would account for these specific features of carbohydrates. Within the framework of a workshop involving the participation of 11 research groups active in the field, several commonly used molecular mechanics force fields and special carbohydrate parameter sets have been considered. The application of 20 force fields and/or sets of parameters to a series of seven test cases provided a fairly general picture of the potentiality of these parameter sets for giving a consistent image of structure and energy of carbohydrate molecules. The results derived from a chemometric analysis (principal component analysis, PCA) give a global view of the performances of the force fields and parameter sets for carbohydrates. The present analysis (i) provides an identification of the parameter sets which differ from the bulk, (ii) helps to establish the relationship that exists between the different parameter sets, (iii) provides indications for selecting different parameter sets to explore the force field dependency (or the lack of thereof) of a given molecular modeling study. Through the PCA, we have created a force field landscape on which the different force fields are related to each other on a relative scale. New carbohydrate force fields can easily be inserted into this landscape (PCA model) and related to the performance of existing force fields.