Structure and Function of Photosystem I–[FeFe] Hydrogenase Protein Fusions: An All-Atom Molecular Dynamics Study

Abstract

All-atom molecular dynamics (MD) simulation was used to study the solution dynamics and protein-protein interactions of protein fusions of photosystem I (PSI) from Thermosynechococcus elongatus and an [FeFe]-hydrogenase (FeFe H2ase) from Clostridium pasteurianum, a unique complex capable of photocatalytic hydrogen production. This study involved fusions of these two proteins via dithiol linkers of different length including decanedithiol, octanedithiol, and hexanedithiol, for which experimental data had previously been obtained. Evaluation of root-mean-squared deviations (RMSDs) relative to the respective crystal structures of PSI and the FeFe H2ase shows that these fusion complexes approach stable equilibrium conformations during the MD simulations. Investigating protein mobility via root-mean-squared fluctuations (RMSFs) reveals that tethering via the shortest hexanedithiol linker results in increased atomic fluctuations of both PSI and the hydrogenase in these fusion complexes. Evaluation of the inter- and intraprotein electron transfer distances in these fusion complexes indicates that the structural changes in the FeFe H2ase arising from ligation to PSI via the shortest hexanedithiol linker may hinder electron transport in the hydrogenase, thus providing a molecular level explanation for the observation that the medium-length octanedithiol linker gives the highest hydrogen production rate.

Unexpected trends in the hydrophobicity of fluorinated amino acids reflect competing changes in polarity and conformation

“…7,8 Understanding how to use amino acid mutations to control the hydrophobic effect is critical to develop new protein-based drugs, biodevices and materials. [9][10][11][12][13] Simultaneously, minimizing changes in solute-solute packing upon mutations is desirable to ensure that protein structureand thus function -is preserved. 14,15 This is, however, difficult with the limited pool of canonical hydrophobic amino acids because their side chains differ in structure and volume.…”

The Multiple Origins of the Hydrophobicity of Fluorinated Apolar Amino Acids

“…Controlling protein thermal stability, resistance against proteolysis, affinity and specificity for ligands, and efficiency of enzymatic activity is indispensable to bring promising protein-based drugs and devices to reality, e.g., antimicrobial peptides as the next-generation antibiotics, 7,8 cell-penetrating peptides to carry drugs into the cell, 9 enzymes for industrial biocatalysis to produce biofuels, biomolecular photovoltaic devices to produce H 2 , or soil nitrification under hypersaline conditions. [10][11][12] To explore the potential of fluorinated peptides and…”

Unexpected Trends in the Hydrophobicity of Fluorinated Amino Acids Reflect Competing Changes in Polarity and Conformation

“…The charges were calculated at the RHF/6-31G* level of theory from a two-step geometry optimization (MP2/6-31G* optimization followed by RHF/6-31G* optimization). Quantum mechanical calculations were performed with the Gaussian 03 software 12 , and RESP fitting of the partial charges was performed with the Antechamber package 13 .…”