# Simulation of Proton Translocation in Biomolecules

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $310,328

## Abstract

PROJECT SUMMARY
 The transport of protons in biomolecular systems is a phenomenon of fundamental importance to processes
such as ATP synthesis, enzyme catalysis, the maintenance of pH gradients, proton pumping, viral infection, and
substrate/ion transport across membranes via protein transporters, symporters, and antiporters. Modeling
biomolecular proton translocation in silico is a significant challenge due to the complex chemical reactions
involved in Grotthuss proton shutting between water molecules and with protonatable amino acids, as well as
the complexity of the target biomolecular systems. In most cases, it is not only important to understand the
mechanism of proton binding and transport, but also its coupling to other mechanistically relevant biomolecular
processes, such as protein conformational changes, substrate binding, other protonation events, and dynamic
hydration.
 In this project the continued development and application of a powerful multiscale computer simulation
methodology is described for the study of proton transport in several key classes of proton translocating
biomolecular systems, including channels (influenza A and B M2 channels), antiporters/symporters (ClC Cl-/H+
antiporter and phosphate transporter, respectively), and transporters (proton-coupled oligopeptide transporter
and EmrE multidrug transporter). The overall research plan is made possible by a novel reactive molecular
dynamics simulation approach integrated with quantum mechanics/molecular mechanics (QM/MM) methods that
allows for the study of explicit long-length and -time scale proton transport through water molecules and ionizable
molecular groups in hydrogen-bonded networks, as well as by new innovations in enhanced free energy
sampling methodology, machine learning, kinetic network theory, and coarse-graining. A primary goal in the
research with this methodology in hand is to reveal the mechanisms of proton transport, as well as its coupling
to hydration and conformational changes, in the above mentioned biomolecular systems. All of these studies will
be carried out in collaboration with leading experimentalists, while continuing to add a new dimension to the field
of biomolecular computer simulation as a whole.
1

## Key facts

- **NIH application ID:** 9934213
- **Project number:** 5R01GM053148-23
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Gregory A. Voth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $310,328
- **Award type:** 5
- **Project period:** 1996-05-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934213

## Citation

> US National Institutes of Health, RePORTER application 9934213, Simulation of Proton Translocation in Biomolecules (5R01GM053148-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934213. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*