Using AMOEBA to Uncover Deformation and Hydration Anisotropy in Collagen-Mimetic Peptides

Collagen is the primary constituent of the supramolecular fibers found in connective tissues. To be able to predict collagen's properties, we need rigorous characterization at the molecular scale. In this work, we focus on collagen-mimetic peptides (CMPs) that are composed of short sequences of (PPG) tripeptides folded into a triple helix. We use molecular dynamics simulations with the AMOEBA polarizable force field to model these CMPs at physiological temperature. We show that AMOEBA captures length-dependent fraying of the triple helix, consistent with experimental observations. We also introduce new metrics to quantify the deformation of the triple helix and hydration dynamics. This enables a systematic quantification of CMPs under a variety of conditions, which was missing in the field. We apply our approach to mutated CMPs and CMPs in the presence of d-glucose. We find that translational diffusion anisotropy is a molecular signature of CMP structural integrity.