Abstract
A binding event between two proteins typically consists of a diffusional search of binding partners for one another, followed by a specific recognition of the compatible binding sites resulting in the formation of the complex. However, it is unclear how binding partners find each other in the context of the crowded, constantly fluctuating, and interaction-rich cellular environment. Here we examine the non-specific component of protein-protein interactions, which refers to those physicochemical properties of the binding partners that are independent of the exact details of their binding sites, but which can affect their localization or diffusional search for one another. We show that, for a large set of high-resolution experimental 3D structures of binary, transient protein complexes taken from the DOCKGROUND database, the binding partners display a surprising, statistically significant similarity in terms of their total hydration free energies normalized by a size-dependent variable. We hypothesize that colocalization of binding partners, even within individual cellular compartments such as the cytoplasm, may be influenced by their relative hydrophilicity, potentially in response to local hydrophilic gradients.
Highlights
From signal transduction cascades to enzymatic activation, from antibody-antigen recognition to cellular trafficking, direct noncovalent protein-protein interactions are the central pillar supporting most of biological functional activity on the molecular level [1]
After performing additional short relaxation molecular dynamics (MD) simulations of each of the binding partners, we evaluated for each of them different geometric properties such as solvent-accessible surface area, radius of gyration, and volume, or different physicochemical properties such as total charge, isoelectric point, hydration free energy (HFE), and total electrostatic energy (EE)
We focus first on the subset containing 118 eukaryotic proteins (59 pairs) interacting in the cytoplasm or nucleoplasm
Summary
From signal transduction cascades to enzymatic activation, from antibody-antigen recognition to cellular trafficking, direct noncovalent protein-protein interactions are the central pillar supporting most of biological functional activity on the molecular level [1]. Pairs of interacting partners were classified into different subsets based on their origin and the known site of complex formation in the cell or extracellular space, following the detailed characterization of the entire set of 268 proteins (Table S1).
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