This study reports first principle calculations and molecular mechanics calculations of glutathione and its fragments with the goal of determining whether the conformational nature of this tripeptide can be inferred based on the geometries of its constituents. Although the size of a molecule usually predetermines the applicable computational methodology (i.e., molecular mechanics or first principles), a combinatory approach that utilizes the advantages of both methods is useful to facilitate modelling of large molecular systems. (C) 2011 Elsevier B.V. All rights reserved.