Conformational analyses of some thiamin-related compounds have been performed in order to find the relationship between their conformational and biochemical properties. Relaxed 2-D potential energy maps of free thiamin, its antagonists, and C(2) adducts were obtained using the molecular mechanics (MM) method. The antagonists include 4’-deaminothiamin, oxythiamin, pyrithiamin, thiamin thiazolone, thiamin thiothiazolone, 6’-methyl-4H-thiamin and 6’-methylthiamin, and the C(2) adducts include 2-(alpha-hydroxyethyl)thiamin (HET), 2-(alpha-lactyl)thiamin (LT), 6’-methyl-4H-lactylthiamin and 6’-methyllactylthiamin. All of the local minima conformers were also identified for the active intermediates LT and HET. In numerous crystal structures, free thiamin assumes mostly the F form and less frequently the S form. The C(2) adducts assume only the S form. However, neither thiamin nor its active intermediates are found in the V form in crystal, but the cofactor assumes the V form in the active site of the protein. The MM map of free thiamin shows that the F form is truly the global minimum, while the S form occupies another minimum slightly higher in energy and lower in existence probability than the F form. The V form is also a local minimum but with very low existence probability. In addition, the availability of only one 4’-amino H atom for the intermolecular hydrogen bond makes it very unlikely that the thiamin molecule assumes the V form in solution and thereby in crystals. For various antagonists, either the V form is the global minimum or its existence probability is higher than that of thiamin. The V form instead of the crystalline S form is the global minimum conformer for both LT and HET. However, the V form of the C(2) adducts also would not bc observed in the crystalline state due to the conformational characteristics of free thiamin; their V forms accordingly may be unique conformers available only inside the protein but not in solution. Based on the results of MM calculations and the crystal structures of holoenzymes, it is proposed that the active conformers of both intermediates are V forms with an intramolecular N-H...O(hydroxyl) hydrogen bond. A putative stereochemical model for thiamin catalysis is presented in which N-H...O hydrogen bonds contribute to the acceleration of the enzymic reaction by lowering the energies of the various species occurring along the reaction path. The principles of least motion and maximum orbital overlap which were originally applied to the decarboxylation reaction for the intermediates in the S form still hold for the V form.