Related Experiment Video
Updated: May 9, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Molecular origins of binding affinity: seeking the Archimedean point
Panagiotis L Kastritis1, Alexandre M J J Bonvin
1Bijvoet Center for Biomolecular Research, Science Faculty - Chemistry, Utrecht University, 3584CH Utrecht, The Netherlands.
Abstract:
Connecting three dimensional structure and affinity is analogous to seeking the 'Archimedean point', a vantage point from where any observer can quantitatively perceive the subject of inquiry. Here we review current knowledge and challenges that lie ahead of us in the quest for this Archimedean point. We argue that current models are limited in reproducing measured data because molecular description of binding affinity must expand beyond the interfacial contribution and also incorporate effects stemming from conformational changes/dynamics and long-range interactions. Fortunately, explicit modeling of various kinetic schemes underlying biomolecular recognition and confined systems that reflect in vivo interactions are coming within reach. This quest will hopefully lead to an accurate biophysical interpretation of binding affinity that would allow unprecedented understanding of the molecular basis of life through unraveling the why's of interaction networks.
Related Concept Videos
The Equilibrium Binding Constant and Binding Strength
The Equilibrium Binding Constant and Binding Strength
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
