Molecular origins of binding affinity: seeking the Archimedean point

- Structure-based prediction of Kd's for complexes is qualitative and limited to near-rigid binders.
- Both buried surface area and global non-interacting surface properties relate to Kd.
- Conformational change and dynamics have a major effect on structure-affinity relationships.
- Obtaining Kd data measured in vivo for various kinetic schemes will be essential.