Additivity Principles in Biochemistry

We cannot yet reliably fold proteins or RNA molecules by computer, predict ligand binding affinities, compute conformational transitions, or use the sequence information in the Human Genome very effectively to understand biomolecular function and disease. Why not? Perhaps some of our models in computational biology are based on flawed assumptions. Thermodynamic additivity principles are the foundations of chemistry, but few additivity principles have yet been found successful in biochemistry.