Million-atom molecular dynamics simulations reveal the interfacial interactions and assembly of plant PSII-LHCII...

Protein-protein interface interactions dictate efficient excitation energy transfer from light-harvesting antennas to the photosystem II (PSII) core. In this work, we construct a 1.2 million atom-scale model of plant C₂S₂-type PSII-LHCII supercomplex and perform microsecond-scale molecular dynamics (MD) simulations to explore the interactions and assembly mechanisms of the sizeable PSII-LHCII supercomplex. We optimize the nonbonding interactions of the PSII-LHCII cryo-EM structure using microsecond-scale MD simulations. Binding free energy calculations with component decompositions reveal that hydrophobic interactions predominantly drive antenna-core association and the antenna-antenna interactions are relatively weak. Despite the positive electrostatic interaction energies, hydrogen bonds and salt bridges mainly provide directional or anchoring forces for interface binding. Analysis of the roles of small intrinsic subunits of PSII suggests that LHCII and CP26 first interact with small intrinsic subunits and then bind to the core proteins, whereas CP29 adopts a one-step binding process to the PSII core without the assistance of other factors. Our study provides insights into the molecular underpinnings of the self-organization and regulation of plant PSII-LHCII. It lays the framework for deciphering the general assembly principles of photosynthetic supercomplexes and possibly other macromolecular structures. The finding also has implications for repurposing photosynthetic systems to enhance photosynthesis.