Molecular mechanism underlying conformations and region communications of periplasmic receptor affected by diversity...

The periplasmic receptor (XAC2383) exhibits a notable affinity for phosphate ligands, undergoing conformational changes upon their binding. Understanding the molecular mechanisms behind this preference is crucial for a comprehensive grasp of XAC2383's function. In this study, Gaussian accelerated molecular dynamics (GaMD) simulations in conjunction with Markov state models (MSMs) and communication pathway analysis were applied to investigate the ligand-induced effects on the conformational dynamics of XAC2383. Our analysis of the MSMs indicates that the three phosphate ligands (PO₄, POP, and ATP) induce fewer conformation states and significantly alter the conformations of loops L1-L5 and the β2-L-α2 region compared to the ligand-free APO form of XAC2383. This finding is corroborated by our principal component analysis (PCA). Communication pathway analyses further reveal that binding of these ligands modifies the communication pathways observed in APO XAC2383, establishing direct communications between the two lobes via L1, α6, α7, and α9. Interaction fingerprint analysis highlights that residue K193 is a key player, shared among the interaction fingerprints of all three ligands, and is essential for regulating the communication networks. Collectively, our findings offer valuable insights into the functional mechanisms of XAC2383.