Small Molecules Have More Information per Atom Than Biologics
A comparative analysis finds that small-molecule drugs carry significantly more information per atom than biologics, based on Shannon entropy calculations from molecular weight and atom counts. This suggests fundamental structural and data-density differences between the two drug classes, with implications for informatics and drug discovery.
Background
- The article comes from Corin Wagen, a chemist who blogs about drug discovery and molecular design. He often challenges conventional wisdom in pharmaceutical research.
- "Small molecules" are traditional drugs (e.g., aspirin) — simple chemical compounds with low molecular weight. "Biologics" are large, complex molecules like antibodies or proteins made in living cells (e.g., Humira, insulin).
- The key metric is "information per atom": the author argues that because small molecules are built more densely with functional groups, each atom carries more specific chemical information (binding interactions, shape, reactivity) than the atoms in a biologic.
- This matters for the ongoing debate in pharma over whether to invest in small-molecule drugs (easier to manufacture, can be taken orally) or biologics (often more potent, but expensive and injectable). The piece flips the usual framing, which treats biologics as inherently "more informational" due to their size.