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Theta-Defensin Proteins: Conformational Variability and Environmental Effects
Nicolas Vatiliotis1, Finn van Loon1, Doğa Selin Damar1,2
1Computational Biotechnology, RWTH Aachen University, 52074 Aachen, Germany.
Abstract:
Theta-defensins are a unique class of cyclic antimicrobial peptides known for their exceptional structural stability and broad-spectrum antimicrobial activity. Despite their therapeutic potential in mammals, the effects of solvent environments and specific mutations on their conformational stability remain poorly understood. This paper employs all-atom molecular dynamics simulations under different solvent conditions to investigate the structural dynamics of baboon theta-defensin-2 (BTD-2) peptides, as well as solvent effects. BTD-2 was selected due to its higher arginine content, enhancing its antimicrobial potency compared to that of the rhesus theta-defensin-1 protein. We compare the dynamics of 3 different BTD-2 conformations and assess their flexibility, residual fluctuations, and thermal stability. Although similar in sequence, these peptides provide conformation-specific temporal characteristics. The insights gained through the analysis of the simulation data contribute to a deeper understanding of theta-defensin stability, providing important information related to the rational design of peptide-based antimicrobial and antiviral therapeutics.
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