Enabling Precise Simulations of Paramagnetic Relaxation Enhancement

Objective

PREcise – Enabling Precise Simulations of Paramagnetic Relaxation Enhancement – addresses a long-standing challenge in structural biology: the quantitative interpretation of Paramagnetic Relaxation Enhancements (PREs) in metalloproteins. Nearly half of all proteins coordinate or interact with metal cofactors, whose roles in electron transfer, catalysis, oxygen binding, and structural stabilization are fundamental to life. Understanding these systems requires accurate characterization of their coordination chemistry and dynamic properties. However, metal centers’ complex electronic structures make them difficult to study with standard structural biology methods. Spectroscopic techniques, particularly paramagnetic NMR, offer unique insights into their local environment, with PREs being among the most sensitive probes. Yet, despite their potential, PREs lack a reliable Quantum Chemistry-based framework for quantitative interpretation, limiting their impact. PREcise aims to bridge this gap by integrating advanced spin relaxation theory with state-of-the-art quantum chemical calculations to deliver the first predictive, first-principles protocol for nuclear relaxation in open-shell bioinorganic systems. Building on recent methodological advances in the modeling of paramagnetic materials, we will first apply the approach to well-characterized transition metal complexes before scaling to complex biomolecular targets. This synergy between quantum theory, spectroscopy, and coordination chemistry will unlock the structural and dynamic information hidden in PRE data, enabling more accurate models of metalloproteins. The outcomes will pave the way for new insights into bioinorganic function, with potential applications in drug design, bio-inspired catalysis, and materials science.