About this Research Topic
Living cells need a continuous energy supply to sustain their metabolism and perform vital biological functions. Heme proteins’ physiological importance as redox-active components involved in various electron and proton transfer reactions has drawn substantial research interest in enzymology, bioenergetics, and structural and molecular biology. Heme-proteins represent a vast group of enzymes, and the heme cofactor located in their active center plays a pivotal role in performing a wide range of biochemical functions, such as electron transfer (cytochromes), catalysis (catalases, peroxidases), detoxification (cytochrome P450), transport and storage of small molecules (hemoglobin, myoglobin), proton-pumping and energy transduction (cytochrome oxidases, nitric-oxide reductases). Computer modeling, simulations, and experiments are used to understand their molecular mechanisms and catalytic reactions better. By studying how these biomolecules work, researchers can design more efficient drugs or inhibitors and develop more effective treatments for heme-proteins dysfunction-related disorders. Synthetic bioinspired heme proteins are valuable model systems in structural/functional studies and have potential for various biomedical and bionanotechnological applications. Moreover, synthetic redox proteins with precisely designed electrochemical properties could be employed in biosensors and bioelectronic devices for amperometric biosensing, biocatalytic, and biofuel cell applications.
This Research Topic explores heme proteins’ structural and functional diversity using both computational and experimental methods. The focus is on the bioenergetic and kinetic aspects of the reaction mechanisms and catalytic functions of this group of proteins and enzymes. In these systems, the coupling of electron (ET) and proton transfer (PT) reactions, including the Bohr-redox effect, often plays a central role. Moreover, examining protein-cofactor interactions in detail in native and synthetic heme proteins would provide a better understanding of structure-function interrelationships. Advanced experimental techniques like high-resolution crystallography, cryo-EM, NMR, site-specific mutagenesis, kinetic electrometric measurements, time-resolved optical spectroscopies, kinetic isotope effects, and EPR analyses are the methods of choice, combined with multiscale computer simulations utilizing high-performance clusters and supercomputers. Additionally, phylogenetic and structural analyses can be applied to provide more details about the origin, evolutionary aspects, similarity, and diversity of heme proteins by using bioinformatics tools. Health-related issues caused by the dysfunction of heme proteins, including clinically relevant mutations or mitochondrial abnormalities, such as sickle cell anemia and neurodegenerative diseases like Alzheimer's and Parkinson's, may also be addressed. The scope of this Research Topic highlights the latest and promising research trends covering various aspects of cytochromes and other heme proteins.
We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Modeling and simulations of metalloporphyrin enzymes and their catalytic molecular mechanisms
• Thermodynamics and kinetics of chemical processes in heme proteins
• Exploring the coupling of electron and proton transfer reactions and proton pumping function in biology by theory, computation, and experiments
• Protein-cofactor interactions in natural and bioinspired heme-protein structures
• Assessing the role of solvation and conformational dynamics by experimental and computational methods
• Cytochrome P450 enzymes and substrate/drug metabolism
• Protein nanowires comprised of multi-heme cytochromes and long-range electron transfer
• Synthesis, characterization, and analysis of artificial heme proteins
• Biosensors with heme proteins
• Novel multiscale computational approaches (incl. hybrid QM/MM, QM/MD, QM/SCE methods, and AI/ML-based approaches)
• Advanced experimental techniques (incl. high-resolution crystallography, Cryo-EM, NMR, kinetic electrometric measurements, time-resolved optical spectroscopies)
• Phylogenetic and structural analysis of heme proteins and specific subgroups
• The dysfunction of heme-proteins, including harmful mutations associated with severe health conditions
This Research Topic explores heme proteins’ structural and functional diversity using both computational and experimental methods. The focus is on the bioenergetic and kinetic aspects of the reaction mechanisms and catalytic functions of this group of proteins and enzymes. In these systems, the coupling of electron (ET) and proton transfer (PT) reactions, including the Bohr-redox effect, often plays a central role. Moreover, examining protein-cofactor interactions in detail in native and synthetic heme proteins would provide a better understanding of structure-function interrelationships. Advanced experimental techniques like high-resolution crystallography, cryo-EM, NMR, site-specific mutagenesis, kinetic electrometric measurements, time-resolved optical spectroscopies, kinetic isotope effects, and EPR analyses are the methods of choice, combined with multiscale computer simulations utilizing high-performance clusters and supercomputers. Additionally, phylogenetic and structural analyses can be applied to provide more details about the origin, evolutionary aspects, similarity, and diversity of heme proteins by using bioinformatics tools. Health-related issues caused by the dysfunction of heme proteins, including clinically relevant mutations or mitochondrial abnormalities, such as sickle cell anemia and neurodegenerative diseases like Alzheimer's and Parkinson's, may also be addressed. The scope of this Research Topic highlights the latest and promising research trends covering various aspects of cytochromes and other heme proteins.
We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Modeling and simulations of metalloporphyrin enzymes and their catalytic molecular mechanisms
• Thermodynamics and kinetics of chemical processes in heme proteins
• Exploring the coupling of electron and proton transfer reactions and proton pumping function in biology by theory, computation, and experiments
• Protein-cofactor interactions in natural and bioinspired heme-protein structures
• Assessing the role of solvation and conformational dynamics by experimental and computational methods
• Cytochrome P450 enzymes and substrate/drug metabolism
• Protein nanowires comprised of multi-heme cytochromes and long-range electron transfer
• Synthesis, characterization, and analysis of artificial heme proteins
• Biosensors with heme proteins
• Novel multiscale computational approaches (incl. hybrid QM/MM, QM/MD, QM/SCE methods, and AI/ML-based approaches)
• Advanced experimental techniques (incl. high-resolution crystallography, Cryo-EM, NMR, kinetic electrometric measurements, time-resolved optical spectroscopies)
• Phylogenetic and structural analysis of heme proteins and specific subgroups
• The dysfunction of heme-proteins, including harmful mutations associated with severe health conditions
Keywords: Bioenergetics, Computer Simulations, Experimental Methods, Enzyme Reaction Mechanism, ET/PT, Proton Pumping, Phylogenetics, Proteinopathy
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
