has been validated by predicting novel structures and subsequently verifying the predictions by X-ray structure determination. The force field has been useful in relating details of the structures of alkylcobalamins to the lability of the Co -C bond towards bond homolysis, probing the conformational flexibility of the 5%-deoxyadenosyl ligand in adenosylcobalamin (AdoCbl, coenzyme B 12 ), and studying the conformation of coenzymatically active AdoCbl analogs, including one that fails to crystallize. The technique has been further extended to include the use of NMR-derived distance restraints in molecular dynamics (MD) and simulated annealing (SA) procedures. This methodology permits for the first time a detailed description of the motions of cobalt corrins in solution. The consensus structures of SA calculations agree well with the known solid state structures of two complete cobalamins (CH 3 Cbl and CNCbl), including, importantly, the corrin fold angle. The base-off analogs have significantly smaller corrin fold angles, implying that base-on Cbls are under steric strain. These observations lend credence to proposals for the enzymatic labilization of the Co-C bond involving upward flexing of the corrin ring. Preliminary results on the modeling of coenzyme B 12 (AdoCbl) in solution are reported.