Steven Fried

All Publications

• Environment- and Conformation-Induced Frequency Shifts of C-D Vibrational Stark Probes in NAD(P)H Cofactors. The journal of physical chemistry letters Fried, S. D., Mukherjee, S., Mao, Y., Boxer, S. G. 2024: 10826-10834

  Abstract

  NAD(P)H cofactors are found in all forms of life and are essential for electron and hydrogen atom transfer. The linear response of a carbon-deuterium (C-D) vibration based on the vibrational Stark effect can facilitate measurements of electric fields for critical biological reactions including cofactor-mediated hydride transfer. We find both inter- and intramolecular electric fields influence the C-D frequency in NAD(P)H and nicotinamide-like models where the reactive C4-hydrogen has been deuterated. Hence, the C-D frequency can report both environmental electrostatics and conformational changes of the nicotinamide ring. Conformation-dependent effects are mediated through space as electrostatic effects, rather than through-bond. A Stark tuning rate of 0.57 cm-1/(MV/cm) was determined using both experimental and computational approaches, including vibrational solvatochromism, molecular dynamics simulations, and in silico Stark calculations. The vibrational probe's Stark tuning rate is shown to be robust and suitable for measuring fields along hydride transfer reaction coordinates in enzymes.

  View details for DOI 10.1021/acs.jpclett.4c02497

  View details for PubMedID 39436117

• Hydration and membrane lipids influence rhodopsin activation Hewage, K. K., Chen, S. X., Fried, S. E., Luu, T. N., Struts, A. V., Perera, S. C., Brown, M. F. CELL PRESS. 2024: 515A

  View details for Web of Science ID 001194120703038

• Osmotic stress studies of G-protein-coupled receptor rhodopsin activation. Biophysical chemistry Struts, A. V., Barmasov, A. V., Fried, S. D., Hewage, K. S., Perera, S. M., Brown, M. F. 2023; 304: 107112

  Abstract

  We summarize and critically review osmotic stress studies of the G-protein-coupled receptor rhodopsin. Although small amounts of structural water are present in these receptors, the effect of bulk water on their function remains uncertain. Studies of the influences of osmotic stress on the GPCR archetype rhodopsin have given insights into the functional role of water in receptor activation. Experimental work has discovered that osmolytes shift the metarhodopsin equilibrium after photoactivation, either to the active or inactive conformations according to their molar mass. At least 80 water molecules are found to enter rhodopsin in the transition to the photoreceptor active state. We infer that this movement of water is both necessary and sufficient for receptor activation. If the water influx is prevented, e.g., by large polymer osmolytes or by dehydration, then the receptor functional transition is back shifted. These findings imply a new paradigm in which rhodopsin becomes solvent swollen in the activation mechanism. Water thus acts as an allosteric modulator of function for rhodopsin-like receptors in lipid membranes.

  View details for DOI 10.1016/j.bpc.2023.107112

  View details for PubMedID 37952496

• Carbon-deuterium bonds as reporters of electric fields in solvent and protein environments Fried, S. E., Kirsh, J. M., Zheng, C., Mao, Y., Markland, T. E., Boxer, S. G. CELL PRESS. 2023: 481A

  View details for Web of Science ID 000989629702586

• Carbon-deuterium bonds as reporters of electric fields in solvent and protein environments. Biophysical journal Fried, S. D., Kirsh, J. M., Zheng, C., Mao, Y., Markland, T. E., Boxer, S. G. 2023; 122 (3S1): 481a

  View details for DOI 10.1016/j.bpj.2022.11.2574

  View details for PubMedID 36784478

• Solvent Organization and Electrostatics Tuned by Solute Electronic Structure: Amide versus Non-Amide Carbonyls. The journal of physical chemistry. B Fried, S. D., Zheng, C., Mao, Y., Markland, T. E., Boxer, S. G. 2022

  Abstract

  The ability to exploit carbonyl groups to measure electric fields in enzymes and other complex reactive environments by using the vibrational Stark effect has inspired growing interest in how these fields can be measured, tuned, and ultimately designed. Previous studies have concentrated on the role of the solvent in tuning the fields exerted on the solute. Here, we explore instead the role of the solute electronic structure in modifying the local solvent organization and electric field exerted on the solute. By measuring the infrared absorption spectra of amide-containing molecules, as prototypical peptides, and contrasting them with non-amide carbonyls in a wide range of solvents, we show that these solutes experience notable differences in their frequency shifts in polar solvents. Using vibrational Stark spectroscopy and molecular dynamics simulations, we demonstrate that while some of these differences can be rationalized by using the distinct intrinsic Stark tuning rates of the solutes, the larger frequency shifts for amides and dimethylurea primarily result from the larger solvent electric fields experienced by their carbonyl groups. These larger fields arise due to their stronger p-π conjugation, which results in larger C═O bond dipole moments that further induce substantial solvent organization. Using electronic structure calculations, we decompose the electric fields into contributions from solvent molecules that are in the first solvation shell and those from the bulk and show that both of these contributions are significant and become larger with enhanced conjugation in solutes. These results show that structural modifications of a solute can be used to tune both the solvent organization and electrostatic environment, indicating the importance of a solute-centric paradigm in modulating and designing the electrostatic environment in condensed-phase chemical processes.

  View details for DOI 10.1021/acs.jpcb.2c03095

  View details for PubMedID 35901512

• Tuning solvent electrostatic environment of amide carbonyls as prototypical peptide backbones Fried, S. E., Zheng, C., Mao, Y., Markland, T. E., Boxer, S. G. CELL PRESS. 2022: 186A

  View details for Web of Science ID 000759523001175

• Activation of G-protein-coupled receptors by hydration driven sponge mechanism Fried, S. E., Hewage, K. K., Eitel, A. R., Struts, A. V., Weerasinghe, N., Perera, S. C., Brown, M. F. CELL PRESS. 2022: 458A

  View details for Web of Science ID 000759523003042