Spin Relaxation Rates of Collagen-Associated Water Using Molecular Dynamics Simulations

Abstract Collagenous tissues such as articular cartilage and tendon are central to joint function, and their microstructures are routinely probed using magnetic resonance imaging (MRI). A key feature influencing MRI contrast in these tissues is the spin relaxation behavior of water in the vicinity of collagen, which is also closely linked to the origin of the magic-angle effect. In this study, we use molecular dynamics simulations to investigate the nuclear magnetic resonance spin relaxation rate constants 1/T1 and 1/T2 of water protons near a collagen peptide at room temperature by evaluating the zero-frequency spectral density J(0). A model system consisting of water surrounding a single isolated tropocollagen fragment was employed. To balance the computational cost and statistical accuracy, trajectory data were systematically truncated following a series of tests assessing the relative influence of trajectory length and ensemble size on relaxation estimates for bulk water. The results indicate that the presence of collagen predominantly affects water molecules within the first hydration shell, while outer shells exhibit behavior approaching that of bulk water. Accurate estimation of relaxation rates using standard Redfield theory was found to be challenging because of significant variability in the residence times of water molecules within individual hydration shells, leading to uneven trajectory lengths. To mitigate artifacts arising from this variability, ensemble-averaged spectral density functions were fitted to Lorentzian forms, resulting in an improved stability and accuracy of the computed relaxation rates. Analysis of hydration-shell-resolved dynamics reveals a monotonic decrease in relaxation rates from the first to the third hydration shell, highlighting the strong influence of the protein proximity on water dynamics. These findings demonstrate the sensitivity of spin relaxation to the local hydration structure and provide a computational framework for systematically probing relaxation properties of collagen-associated water in different hydration shells. The approach offers a pathway toward more realistic modeling of fibrillar collagen networks under varying environmental conditions with implications for interpreting MRI contrast in collagen-rich tissues.