Atomistic simulations of the reactive processes in the heme-containing proteins

Heme proteins have a great impact in the protein research. Due to the unique electronic properties of heme these proteins are abundant in nature and have a wide range of biological functions in most of the organisms from archea to eukaryotes. The ability of heme proteins to bind and release small molecules like CO, NO, O2 defines the variety of physiological functions and is related to the structural dynamic properties of the protein matrix surrounding heme.
Cytochrome c oxidase (CcO) is a heme-containing protein, which performs oxygen reduction to water as a part of the membrane complex. Cytochrome c oxidase forms a stable complex with CO in the binuclear heme a3 - Cu(B) active site and is a model system to study ligand binding and release. The pump-probe experiments performed for the CcO-CO system reported the ultrafast dynamics of the CO transfer from the heme Fe to Cu(B) site. Molecular dynamics simulations are used to provide the dynamic structural information during the transfer with atomic resolution. The kinetics of the process determined from the MD simulations is a qualitative agreement with the timescales reported in the experimental studies. The simulations show that the transfer dynamics is ballistic. The doming of the heme Fe observed after the photoexcitation significantly affects the probability of the heme Fe rebinding.
Myglobin (Mb) is an oxygen storage protein, the active site of which contains heme. It allows studying the impact of the structural changes on binding and release of small molecules. The Mb complex with NO was studied using MD simulations. The heme doming effect observed after photodissociation makes the heme Fe less accessible to NO and slows down the rebinding. The DFT parametrized 2A state predicts the existence of the Fe-ON minimum, which is not observable in the experiments, this might be explained by the effect of the 4A PES, that activated during the photoexcitation and that has a lower energy for the configurations corresponding to the Fe-ON minimum.