# Mapping of Electron Tunneling Pathways in Proteins

> **NIH NIH R01** · DUKE UNIVERSITY · 2020 · $324,319

## Abstract

Project Summary
Drug metabolism, programmed cell death, DNA biosynthesis and repair, respiration,
and photosynthesis are familiar biological processes of critical importance to human
health that rely on protein-mediated electron-transfer (ET) reaction mechanisms for
their function. As such, ET pathways lie at the core of life, and the malfunction of ET
pathways is an underlying cause of diseases, notably diseases triggered by oxidative
stress and malfunction of the mitochondrial machinery. Since ET is a process common
to all forms of life, a molecular-level understanding of ET pathways in pathogenic
organisms may be exploited for therapeutic advantage as well. The long-term objective
of this research is to understand, at the molecular, meso, and macro scales, how
biological structure and dynamics influence crucial ET reactions. Theoretical findings
from this laboratory over two decades have discovered how protein structure and
dynamics can modulate ET reaction mechanisms and on the nanometer length scales,
and the laboratory has established widely used methods to predict the corresponding
ET rates. In the last grant period we turned our focus to charge-transport systems that
function on much longer length scales, where grand challenge questions are emerging
regarding ET mechanism and function on the multiple nanometer to the centimeter
length scales. The research proposed here focuses on: (1) the charge hopping
transport on the multiple nanometer scale associated with redox-based signaling and
charge hopping that relieves oxidative stress; (2) charge transport on the micrometer
scale, where the anomalous kinetic signatures discovered in multi-heme extracellular
bacterial appendages will be examined; (3) transport in cable bacteria on the
centimeter scale, where multi-cellular bacterial assemblies with a shared outer
membrane extract energy by bridging physically between reducing and oxidizing
environments, exploiting a common ET conduit that enables collaboration and a
rudimentary demonstration of the benefits of multi-cellularity. A hallmark of this research
program has been its close collaboration between theory and cutting-edge experiment,
and this core approach will continue with intensive collaborations involving Aarhus
University (Denmark), the University of Antwerp (Belgium), the University of California-
Irvine (USA), and Caltech (USA).

## Key facts

- **NIH application ID:** 9971735
- **Project number:** 2R01GM048043-21
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** DAVID BERATAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,319
- **Award type:** 2
- **Project period:** 1993-08-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971735

## Citation

> US National Institutes of Health, RePORTER application 9971735, Mapping of Electron Tunneling Pathways in Proteins (2R01GM048043-21). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9971735. Licensed CC0.

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