Divalent LecA ligands: Boltz-2 structures and MD
Description
Boltz-2 predictions and MD simulations of 5 photoswitchable compounds bridging LecA bacterial lectin dimer
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See the manuscript for full details. Briefly, for each of the five studied molecules in two configurations (E-1 to E-5 and Z-1 to Z-5), 100 structural models of molecules in complex with dimeric lectin LecA were generated using Boltz-2 generative AI model. During the generation of the complexes, Z-isomers were converted to E configuration, yielding only structural models of E-isomers. The top-ranked generated structures were used as input for molecular dynamics (MD) simulations. Protein, ligands and Ca2+ ions were individually prepared according to the StreaMD protocol. Subsequently, 100-ns MD simulations were performed for all E-isomers using the StreaMD toolkit with Gromacs version 2022.3, AMBER 99SB-ILDN.ff force field and TIP3P water model. To obtain structural models of Z-isomers in complex with the LecA dimer, E-isomers were converted using steered MD. A pulling force was applied to the system by modifying the molecular dynamics parameter (MDP) file during a 2-ns MD simulation, affording corresponding Z-isomers in complex with the protein. Finally, MD production runs were carried out for all Z-isomer–LecA complexes, yielding 100-ns XTC trajectories. The analysis of interaction fingerprints in the MD trajectories was done using the ProLIF module, which afforded interaction fingerprint maps.