EXPLORING THE CONFORMATIONAL ENERGY LANDSCAPE OF PROTEINS

Proteins possess a complex energy landscape with a large number of loc al minima called conformational substates that are arranged in a hiera rchical fashion. Here we discuss experiments aimed at the elucidation of the energy landscape in carbonmonoxy myoglobin (MbCO). In the highe st tier of the hierarchy, a few taxonomic substates exist. Because of their small number, these substates are accessible to detailed structu ral investigations. Spectroscopic experiments are discussed that eluci date the role of protonations of amino acid side chains in creating th e substates, The lower tiers of the hierarchy contain a large number o f statistical substates. Substate interconversions are observed in the entire temperature range from below 1 K up to the denaturation temper ature, indicating a wide spectrum of energy barriers that separate the substates.