Speaker
Description
The electrostatic nature of protein pair potentials dictates the fundamental behavior of biological systems, from molecular recognition to the phase stability of highly concentrated formulations. However, accurately quantifying the effective charge state that governs these potentials remains a challenge, as existing methods often fail to reconcile theoretical predictions with experimental reality. I will present a synergistic framework that resolves the underlying forces of protein association by integrating cryogenic electron tomography with amino-acid-level coarse-grained simulations. By isolating the potentials of mean force (PMF) at specific salt concentrations, this combined approach captures pairwise interactions with exceptional accuracy, enabling a determination of the protein charge state that exceeds the precision of current methods.
The results, validated across hen egg-white and human lysozyme as well as bovine serum albumin, show that the alignment between theory and experiment is uniquely sensitive to the protein’s electrostatic environment, while remaining mostly independent of structural variations or non-ionic modifications. Furthermore, the choice of buffer is shown not to be a passive variable but an active modulator of the protein’s effective charge, directly shifting the interaction landscape. This methodology allows for a clear mapping of the transition between long-range electrostatic dominance and the emergence of short-range steric and non-ionic forces. By maintaining proteins in their native solution phase, it provides a robust physical foundation for characterization and predictive modeling of protein behavior in complex chemical environments.