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Abstract Heme is an active center in many proteins. Here we explore computationally the role of heme in protein folding and protein structure. We model heme proteins using a hybrid model employing the AWSEM Hamiltonian, a coarse-grained forcefield for the protein chain along with AMBER, an all-atom forcefield for the heme. We carefully designed transferable force fields that model the interactions between the protein and the heme. The types of protein–ligand interactions in the hybrid model include thioester covalent bonds, coordinated covalent bonds, hydrogen bonds, and electrostatics. We explore the influence of different types of hemes (heme b and heme c) on folding and structure prediction. Including both types of heme improves the quality of protein structure predictions. The free energy landscape shows that both types of heme can act as nucleation sites for protein folding and stabilize the protein folded state. In binding the heme, coordinated covalent bonds and thioester covalent bonds for heme c drive the heme toward the native pocket. The electrostatics also facilitates the search for the binding site.
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This content will become publicly available on July 1, 2025
Controlling heme redox properties in peptide amphiphile fibers with sequence and heme loading ratio
Controlling the reduction midpoint potential of heme B is a key factor in many bioelectrochemical reactions, including long-range electron transport. Currently, there are a number of globular model protein systems to study this biophysical parameter; however, there are none for large polymeric protein model systems (e.g., the OmcS protein from G. sulfurreducens). Peptide amphiphiles, short peptides with a lipid tail that polymerize into fibrous structures, fill this gap. Here, we show a peptide amphiphile model system where one can tune the electrochemical potential of heme B by changing the loading ratio and peptide sequence. Changing the loading ratio resulted in the most significant increase, with values as high as −22 mV down to −224 mV. Circular dichroism spectra of certain sequences show Cotton effects at lower loading ratios that disappear as more heme B is added, indicating an ordered environment that becomes disrupted if heme B is overpacked. These findings can contribute to the design of functional self-assembling biomaterials.
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- Award ID(s):
- 2041751
- PAR ID:
- 10566424
- Editor(s):
- Koder, Ronald
- Publisher / Repository:
- Biophysical Journal
- Date Published:
- Journal Name:
- Biophysical Journal
- Edition / Version:
- 1
- Volume:
- 123
- Issue:
- 13
- ISSN:
- 0006-3495
- Page Range / eLocation ID:
- 1781 to 1791
- Subject(s) / Keyword(s):
- Peptide amphiphiles, Redox Potential, Peptide Materials
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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