A comparative investigation of the consistent valence and extensible systematic force fields. A case study on the conformation of erythromycin A in benzene

Abstract

The performances of the extensible systematic force field (esff), a general purpose force field recently developed for the molecular modeling of inorganic and organometallic compounds, and the well established consistent valence force field (cvff), known for its efficient performances, have been compared in their ability to produce accurately the conformation of organic moieties as well as for their conformational sampling properties. Erythromycin A (Ery-A), a compound with a well established conformation, was selected. After complete assignment of all 1H and 13C resonances of Ery-A in benzene solution, restrained MD simulations based on 44 nOe distance restraints were performed for both esff and cvff force fields, either by immediate application of the restraints on the X-ray structure, or on a set of 50 free MD conformers generated independently. The conformations generated by the two force fields were found to be highly similar, both mutually and to those found previously for Ery-A in the crystalline state and in chloroform. No distance violations larger than 0.22 A were observed. The structures were also validated against 17 non-trivial 3J(1H–1H) coupling constants and 26 3J(13C–1H) coupling constants, the latter determined from gradient-enhanced 1H-{13C} J-HMBC spectra. The conclusion from the present results is that both force fields generate directly comparable conformations for Ery-A.