Water at the Hydrated Membrane-Protein Interface

Abstract

LRP1 is a 600 kDa membrane protein with more than 4500 amino acids and many repeated units, crucial for blood-brain barrier function and possibly implicated in Alzheimer’s disease. We analyze its hydration properties starting from molecular dynamics simulations data produced for all-atom models of the separate units suspended in water. We focus on six amino acids that preserve their position in the units. We show evidence that their average interaction with water depends on the local environment and the 3D protein structure, at least for one of the amino acids. This observation highlights that the hydration property is, in principle, context-dependent and does not depend solely on the hydrophilicity of the amino acid. Therefore, in developing coarse-grained models for large-scale simulations based on effective interactions, our result calls for capturing this feature that could be relevant in large-scale numerical studies of LRP1 within the general context of finding new treatments for neurodegenerative diseases.