大豆リポキシゲナーゼにおける相関運動に基づく残基ネットワーク解析による遠隔熱活性化の解明

Enzyme catalysis has been shown to depend on distal pathways that channel thermal energy from solvent to the active site. In soybean lipoxygenase (SLO), experiments identified a cone-shaped network connecting loop residue Gln322 to Leu546 but not Leu754 in the active site. Here, microsecond molecular dynamics and a correlated motion-based protocol provide an atomistic analysis of such long-range communication. The developed approach enables systematic screening of communication between active site-specific residues that directly contact bound substrate and surface-exposed residues on the protein-solvent interface. In doing so, it provides a deeper molecular insight into experimentally mapped networks by resolving communication trends across diverse conformational ensembles. The simulations recover the experimentally demonstrated thermal initiation loop and the Leu546-directed cone in SLO, exclude the negative-control Ser596, and explain the preference for Leu546 over Leu754 through shorter, more correlated helical pathways. Mutational analysis further reveals the impact of single-site mutations on the network preference between Leu546 and Leu754. These results unify experiments and computation, corroborating an anisotropic channeling of thermal energy in SLO and establishing a general framework for computing distal intra-protein pathways that may enable the thermal activation of enzyme function.