Quantifying the efficiency of principal signal transmission modes in proteins

Fuente: arXiv
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Main Authors: Sahoo, Anil Kumar, Schwarzl, Richard, Miettinen, Markus S., Netz, Roland R.
Format: Preprint
Published: 2024
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author Sahoo, Anil Kumar
Schwarzl, Richard
Miettinen, Markus S.
Netz, Roland R.
author_facet Sahoo, Anil Kumar
Schwarzl, Richard
Miettinen, Markus S.
Netz, Roland R.
contents On the microscopic level, biological signal transmission relies on coordinated structural changes in allosteric proteins that involve sensor and effector modules. The timescales and microscopic details of signal transmission in proteins are often unclear, despite a plethora of structural information on signaling proteins. Based on linear-response theory, we develop a theoretical framework to define frequency-dependent force and displacement transmit functions through proteins and, more generally, viscoelastic media. Transmit functions quantify the fraction of a local time-dependent perturbation at one site, be it a deformation, a force, or a combination thereof, that survives at a second site. They are defined in terms of equilibrium fluctuations from simulations or experimental observations. We apply the framework to our all-atom molecular dynamics simulation data of a parallel, homodimeric coiled-coil (CC) motif that connects sensor and effector modules of a blue-light-regulated histidine kinase from bacterial signaling systems extensively studied in experiments. Our analysis reveals that signal transmission through the CC is possible via shift, splay, and twist deformation modes. Based on the results of mutation experiments, we infer that the most relevant mode for the biological function of the histidine kinase protein is the splay deformation.
format Preprint
id arxiv_https___arxiv_org_abs_2403_12312
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Quantifying the efficiency of principal signal transmission modes in proteins
Sahoo, Anil Kumar
Schwarzl, Richard
Miettinen, Markus S.
Netz, Roland R.
Soft Condensed Matter
Statistical Mechanics
Biological Physics
On the microscopic level, biological signal transmission relies on coordinated structural changes in allosteric proteins that involve sensor and effector modules. The timescales and microscopic details of signal transmission in proteins are often unclear, despite a plethora of structural information on signaling proteins. Based on linear-response theory, we develop a theoretical framework to define frequency-dependent force and displacement transmit functions through proteins and, more generally, viscoelastic media. Transmit functions quantify the fraction of a local time-dependent perturbation at one site, be it a deformation, a force, or a combination thereof, that survives at a second site. They are defined in terms of equilibrium fluctuations from simulations or experimental observations. We apply the framework to our all-atom molecular dynamics simulation data of a parallel, homodimeric coiled-coil (CC) motif that connects sensor and effector modules of a blue-light-regulated histidine kinase from bacterial signaling systems extensively studied in experiments. Our analysis reveals that signal transmission through the CC is possible via shift, splay, and twist deformation modes. Based on the results of mutation experiments, we infer that the most relevant mode for the biological function of the histidine kinase protein is the splay deformation.
title Quantifying the efficiency of principal signal transmission modes in proteins
topic Soft Condensed Matter
Statistical Mechanics
Biological Physics
url https://arxiv.org/abs/2403.12312