AIM: To build a model of 3D-structure of H+, K+-ATPase catalytic subunit for theoretical study and anti-ulcer drug design. METHODS: The model was built on the basis of structural data from the Ca2+-ATPase. Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were se- lected from the protein databank, and amino (N)- and carboxyl (C)-terminal ends were generated as random coil structures. Applying molecular mechanics method then minimized the model energy. Molecular dynamics tech- nique was used to do further structural optimization. RESULTS: The model of 3D-structure of H+, K+-ATPase was derived. The model is reasonable according to several validation criteria. There were ten transmembrane helices (TM1-TM10) in the model and inhibitor-binding site was identified on the TM5-8 riched negatively charged residues. CONCLUSION: The 3D-structure model from our study is informative to guide future molecular biology study about H+, K+-ATPase and drug design based on database searching. AIM: To build a model of 3D-structure of H +, K + -ATPase catalytic subunit for theoretical study and anti-ulcer drug design. METHODS: The model was built on the basis of structural data from the Ca2 + -ATPase. Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were se lected from the protein databank, and amino (N) - and carboxyl (C) -terminal ends were generated as random coil structures. Applying molecular mechanics method then minimized the model energy. Molecular dynamics tech- nique was used to do further structural optimization. RESULTS: The model of 3D-structure of H +, K + -ATPase was derived. There are ten transmembrane helices (TM1-TM10) in the model and inhibitor-binding site was identified on the TM5-8 riched negatively charged residues. CONCLUSION: The 3D-structure model from our study is informative to guide future molecular biology study about H + , K + -ATPase and drug design based on database searching.