Myoglobin ligand gate mechanism analysis by a novel 3D visualization technique

A protein is commonly visualized as a discrete piecewise linear curve, conventionally characterized in terms of the extrinsically determined Ramachandran angles. However, in addition to the extrinsic geometry, the protein has also two independent intrinsic geometric structures, determined by the peptide planes and the side chains respectively. Here we develop a novel 3D visualization method that instead of the extrinsic geometry utilizes the intrinsic geometry of side chains. We base our approach on a series of orthonormal coordinate frames along the protein side chains in combination with a mapping of the atoms positions onto a unit sphere, for visualization purposes. We develop our methodology in terms of an example, by analyzing the acidity dependence of the presumed myoglobin ligand gate. In the literature, the ligand gate is often asserted to be highly localized at the distal histidine, its functioning being regulated by environmental changes. Thus, we investigate whether any pH dependence can be detected in the orientation of the distal and proximal histidine residues, using existing crystallographic data. We observe no pH dependence, in support of the alternative proposals that the ligand gate is more complex and might even be located elsewhere. Our methodology should help the planning of future myoglobin structure experiments, to identify the ligand gate position and its mechanism. More generally, our methodology is designed to visually depict the spatial orientation of side chain covalent bonds in a protein. As such, it can be eventually advanced into a general visual 3D tool for protein structure analysis for purposes of prediction, validation and refinement. It can serve as a complement to widely used visualization suites such as VMD, Jmol, PyMOL and others.