TPSA in Drug Design: Meaning, Thresholds, Why It Matters

By BioDockify Computational Research Team · September 3, 2026 · Concepts

Topological polar surface area explained: what TPSA measures, the 140 A2 threshold for oral absorption, the 90 A2 BBB line, and how to use both in screening.

Read the complete article with tables, code and references on BioDockify.

Key References

• Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem. 2000;43(20):3714-3717. doi:10.1021/jm000942e
• Veber DF, Johnson SR, Cheng HY, et al. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615-2623. doi:10.1021/jm020017n
• RDKit documentation: TPSA calculation via CalcTPSA and the fragment contribution set, rdkit.org.

Scope & Limitations

TPSA is a 2D estimate of a 3D transport property; conformational shielding of polar groups and active transport both create deviations the single number cannot see