An attempt is made to build up a three-dimensional model of squamous cell carcinoma antigen 2 (SCCA2) by means of the homology module of Insight II, where SCCA2 contains the stressed and relaxed forms, i.e. SCCA2(S) and SCCA2(R). The docking of SCCA2(S) with two different target serine proteinases. that are the cathepsin G (Cat G) and the human mast cell chymase (HNIC), are studied theoretically to dive two different complexes. respectively. It is shown, from the molecular surface electricity potential, that in the formation of the two complexes SCCA2(S)-Cat G and SCCA2(S)-HMC, the electrostatic interaction may play ail important role. Since HNIC possesses a loop to produce spatial anti-effect. the complex SCCA2(S)-HMC is less stable than the complex SCCA2(S)-Cat G. However, the reactive site loop involved in SCCA2(S) is an important factor in restraining serine proteinases. (C) 2004 Elsevier Ltd. All rights reserved.