eprintid: 37132
rev_number: 12
eprint_status: archive
userid: 9224
dir: disk0/00/03/71/32
datestamp: 2025-08-28 12:19:26
lastmod: 2025-08-28 13:45:10
status_changed: 2025-08-28 12:19:26
type: doctoralThesis
metadata_visibility: show
creators_name: Hartmann, Eric Hans
title: Developing a Reactive Molecular Simulation Method
for Protein Mechanochemistry
subjects: ddc-540
divisions: i-160001
adv_faculty: af-19
abstract: Collagen has recently been found to form radicals when subjected to mechanical stress, followed by detoxification of DOPA radicals via hydrogen peroxide.
However, it remains unclear how mechanoradicals reach DOPA. Within the
complex environment of the collagen fibril, numerous different reactions are
possible, including hydrogen atom transfer (HAT).
In this work a combined molecular dynamics (MD) and kinetic Monte Carlo
(KMC) method is implemented within an adaptive KMC framework. The developed software, KIMMDY, is capable of simulating long timescale trajectories of reactive condensed phase systems. More than 600 HAT reactions are
simulated in a collagen fibril model with up to 20 consecutive reactions.
To make MD simulations of amino acid radicals possible, a highly accurate
classical force field is trained on QM energies and forces using the Grappa
method. Furthermore, a graph neural network is adapted to predict HAT
rates for ensembles generated from MD simulations in a novel approach to
transition path sampling.
These three methodological advances facilitate the application of reactive
simulations in the collagen fibril to observe HAT pathways from the homolysis
site to the post-translational oxidation product of phenylalanine and tyrosine,
DOPA. The DOPA radical can be observed in simulations and kinetic properties confirm the radical scavenger role. Another radical scavenger, pyridinoline (PYD) is proposed and its mechanochemical properties characterised.
KIMMDY provides a new perspective on radical reactions in collagen and is
designed to be applied to novel molecules and reactions
date: 2025
id_scheme: DOI
id_number: 10.11588/heidok.00037132
ppn_swb: 1934944351
own_urn: urn:nbn:de:bsz:16-heidok-371324
date_accepted: 2025-08-07
advisor: HASH(0x561f65db19d0)
language: eng
bibsort: HARTMANNERDEVELOPING2025
full_text_status: public
place_of_pub: Heidelberg
citation:   Hartmann, Eric Hans  (2025) Developing a Reactive Molecular Simulation Method for Protein Mechanochemistry.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/37132/1/Hartmann_Eric_komplett.pdf