Molecular dynamics simulations of proteins starting from their atomic coordinates have contributed considerably to our understanding of the role of motions in stability and molecular recognition 1 Case D.A. Karplus M. J. Mol. Biol. 1979; 132: 343-368 Crossref PubMed Scopus (390) Google Scholar , 2 Brooks III, C.L. Karplus M. Pettitt B.M. Proteins: a Theoretical Perspective of Dynamics, Structure and Thermodynamics. Adv. Chem. Phys. Wiley, 1998 Google Scholar . However, because of the complexity of the computational problem, the timespan that can be explored is limited (picoseconds–nanoseconds in duration) and is short in comparison with the times characteristic of biochemical processes (microseconds–seconds in duration). The significance of a biochemical reaction in a Darwinian selection process depends on the physiological effect of that reaction. How the motions of a protein on a picosecond timescale contribute to survival of an organism might therefore not be immediately apparent; in fact, many researchers believe that it has no ‘survival value’. However, it is accepted that delivery of oxygen to tissues is vital for (evolutionary) fitness and thus is an important component of natural selection. Apart from the more complex allosteric regulation characteristic of haemoglobin (Hb), the stability of the O2–iron complex towards autoxidation and the rate of ligand dissociation are essential ingredients for physiologically competent O2 delivery 3 Antonini E. Brunori M. Hemoglobin and Myoglobin in their Reactions with Ligands. North Holland Publishing, 1971 Google Scholar , 4 Perutz M.F. Annu. Rev. Physiol. 1990; 52: 1-25 Crossref PubMed Google Scholar ; the latter requires control of the rate of O2 dissociation within rather narrow limits (∼1–100 s−1). Here, we review the role of picosecond motions of side chains in the active site of myoglobin (Mb) in control of the overall rate of O2 dissociation, discussing novel structural and dynamic information obtained from studies of a mutant of sperm whale Mb, Mb-YQR.