UC Davis

Myoglobin was the first protein to have its structure solved, making it one of the longest studied proteins on Earth. Found in the muscle tissues throughout much of the animal kingdom, myoglobin (Mb) is used as a classic example for learning about the relationship between structure and function in proteins. It’s well understood that Mb is strictly an oxygen storage and transport protein. Or is it? The “structure dictates function” school of thought for Mb was brought into question most remarkably when modified mice completely devoid of Mb showed no apparent deficit from the wild type (Garry et al. 1998; Godecke et al. 1999). Now, myoglobin is debated by the scientific community when it comes to function. These revelations lead to the formation of new schools of thought about Mb’s function, with theories ranging from nitric oxide regulation to fatty acid (FA) interactions involved in the electron transport chain (ETC). Studies have shown that Mb interacts with FA specifically and non-specifically in its oxygenated state. Further studies have shown a possibility of chain length dependence on this interaction. Some studies have suggested a possible interaction with nonenal (HNE) enhanced autoxidation or even oxidation by electron transfer of Mb. Although more recent research has found HNE not to be the causative agent they also suggest a different possible suspect for Mb enhancement. To elucidate which theories about Mb’s function hold scientific merit, molecular docking was done with AutoDock 4 using hydrated docking protocols on different physiological states of Mb with various ligands including FAs, HNE, and Cytochrome C (CytC). These docking simulations were used to confirm corresponding NMR data and to predict and validate potential binding sites for these ligands on Mb. Multiple simulation box sizes were tested to reduce the likelihood of biasing results towards a particular binding site, starting with a global full box size that encompassed the entire Mb macromolecule and progressively narrowed in on sites of interest. AutoDock simulations were conducted for Mb from different species, namely from sperm whale (Physeter catodon) and horse heart (Equus caballus), to discern any preferential binding differences.