Surface residues dynamically organize water bridges to enhance electron transfer between proteins

TL;DR

This study uses molecular dynamics simulations to show how surface residues and water bridges facilitate electron transfer between proteins, revealing the importance of solvent organization and structural features in biological ET processes.

Contribution

It introduces a detailed analysis of how surface residues and water bridges influence electronic coupling in protein complexes, highlighting the role of a 'molecular breakwater' in stabilizing water-mediated ET pathways.

Findings

Water bridges enhance electronic coupling in protein complexes.

Mutations disrupting the breakwater reduce ET efficiency.

Surface residues control interprotein solvent dynamics.

Abstract

Cellular energy production depends on electron transfer (ET) between proteins. In this theoretical study, we investigate the impact of structural and conformational variations on the electronic coupling between the redox proteins methylamine dehydrogenase and amicyanin from Paracoccus denitrificans. We used molecular dynamics simulations to generate configurations over a duration of 40ns (sampled at 100fs intervals) in conjunction with an ET pathway analysis to estimate the ET coupling strength of each configuration. In the wild type complex, we find that the most frequently occurring molecular configurations afford superior electronic coupling due to the consistent presence of a water molecule hydrogen-bonded between the donor and acceptor sites. We attribute the persistence of this water bridge to a "molecular breakwater" composed of several hydrophobic residues surrounding the acceptor site. The breakwater supports the function of nearby solvent-organizing residues by limiting the exchange of water molecules between the sterically constrained ET region and the more turbulent surrounding bulk. When the breakwater is affected by a mutation, bulk solvent molecules disrupt the water bridge, resulting in reduced electronic coupling that is consistent with recent experimental findings. Our analysis suggests that, in addition to enabling the association and docking of the proteins, surface residues stabilize and control interprotein solvent dynamics in a concerted way.