On the role of thermal backbone fluctuations in myoglobin ligand gate dynamics

摘要

We construct an energy function that describes the crystallographic structureof spermwhale myoglobin backbone. As a model in our construction, we use theProtein Data Bank entry 1ABS that has been measured at liquid heliumtemperature. Consequently the thermal B-factor fluctuations are very small,which is an advantage in our construction. The energy function that we utilizeresembles that of the discrete non-linear Schrodinger equation. Likewise, ourssupports solitons as local minimum energy configurations. We describe the 1ABSbackbone in terms of solitons with a precision that deviates from 1ABS by anaverage root-mean-square distance, which is less than the experimentallyobserved Debye-Waller B-factor fluctuation distance. We then subject themultisoliton solution to extensive numerical heating and cooling experiments,over a very wide range of temperatures. We concentrate in particular totemperatures above 300K and below the theta-point unfolding temperature, whichis around 348K. We confirm that the behavior of the multisoliton is fullyconsistent with Anfinsen's principle, up to very high temperatures. We observethat the structure responds to an increase of temperature consistently in avery similar manner. This enables us to characterize the onset of thermallyinduced conformational changes in terms of three distinct backbone ligandgates. One of the gates is made of the helix F and the helix E. This is apathway that is presumed to have a major role in ligand migration between theheme and the exterior. The two other gates are chosen similarly, when open theyprovide a direct access route for a ligand to reach the heme. We find that outof the three gates we investigate, the one which is formed by helices B and Gis the most sensitive one to thermally induced conformational changes. Ourapproach provides a novel perspective to the important problem of ligandmigration.