Mechanisms of Peptide Oxidation by Hydroxyl Radicals: Insight at the Molecular Scale

Abstract

Molecular dynamics (MD) simulations were performed to provide atomic scale insight in the initial interaction between hydroxyl radicals (OH) and peptide systems in solution. These OH radicals are representative reactive oxygen species produced by cold atmospheric plasmas. The use of plasma for biomedical applications is gaining increasing interest, but the fundamental mechanisms behind the plasma modifications still remain largely elusive. This study helps to gain more insight in the underlying mechanisms of plasma medicine, but is also more generally applicable to peptide oxidation, of interest for other applications. Combining both reactive and non-reactive MD simulations, we are able to elucidate the reactivity of the amino acids inside the peptide systems and their effect on their structure up to 1 s. Additionally, experiments were performed, treating the simulated peptides with a plasma jet. The computational results presented here correlate well with the obtained experimental data and highlight the importance of the chemical environment for the reactivity of the individual amino acids, so that specific amino acids are attacked in higher numbers than expected. Furthermore, the long timescale simulations suggest that a single oxidation has an effect on the 3D conformation due to an increase in hydrophilicity and intra-and intermolecular interactions.

Oxidant and Antioxidant Effects of Gentisic Acid in a 177Lu-Labelled Methionine-Containing Minigastrin Analogue

“…These species could be molecules with less damage than the previous group, originating from the oxidation, peroxidation and/or cleavage of different side chains of the LMG, not considering the Met residue, which was preserved by the addition of the same amino acid during the radiolabelling procedure. If it is considered that amino acids with aromatic groups act as radical-scavengers and, therefore, are susceptible to oxidation [ 8 , 14 , 16 , 17 ], the amino acids tyrosine (Tyr), tryptophan (Trp), phenylalanine (Phe) and both histidines (His) from H2MG11, would be subject of diverse modifications that could explain several of the impurities detected in this group.…”

Molecular Effects and Tissue Penetration Depth of Physical Plasma in Human Mucosa Analyzed by Contact- and Marker-Independent Raman Microspectroscopy

“…51 Moreover, CAP treatment was associated with visible changes in the cytoskeleton, represented by a coarsening and rearrangement of the actin components, most likely being the result of CAP-dependent protein modifications. 51,58,59 Changes in cell structure morphology and biochemical modifications of molecules due to CAP treatment can be identified by Raman microspectroscopy. Many different biochemical and molecular plasma effects may be responsible for plasma-driven antiproliferation.…”

Plasma for cancer treatment: How can RONS penetrate through the cell membrane? Answers from computer modeling

“…Typically, it can handle a few thousand atoms on time scales of tens of picoseconds. DFTB has been applied in the context of plasma medicine to study the interaction of ROS with the head group of the PLB [32], a specific protein (P-glycoprotein) [37] and peptides [38], as well as the behaviour of O and OH in water [39]. Classical reactive MD simulations, which are based on classical force fields, can typically handle much larger systems and longer time scales compared to DFT or DFTB calculations, ranging from 10 4 to 10 6 atoms, at a time scale in the order of 1 ps -100 ns, depending on the complexity of the interatomic potential.…”