De Novo Hydration of Cryo-EM Reconstructions through Molecular Dynamics Simulations of the Excess Chemical Potential.

ABSTRACT: Predicting the precise positions of water molecules at the protein interface remains a formidable challenge, fueling active research in this field. Here, we present a novel approach based on molecular dynamics simulations that utilizes statistical thermodynamic signatures of water at protein interfaces to improve the accuracy of water placement in cryo-EM maps, with apoferritin as a model benchmark system. The interaction energy of solvent with the protein is insufficient to distinguish between high- and lower-consensus water positions, consistent with reports of earlier work. Instead, we employ a detailed statistical thermodynamic analysis based on the excess chemical potential (WT) - a measure of the thermodynamic balance between the interaction energy of an interfacial water molecule wi

SUBMITTER: Sun Q 

PROVIDER: S-EPMC12139794 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature