Molecular dynamics simulation study of the vanillate transport channel of Opdk

Most water-soluble and small molecules are taken up by substrate-specific channels belonging to the Gram-negative bacteria. The protein named OpdK, a member of OprD family, plays an important role in transporting the vanillate as the only carbon source of Pseudomonas aeruginosa. P. aeruginosa infections can be serious due to the high intrinsic antibiotic resistance owing to the present of the OprD family. We applied standard molecular dynamics, steered molecular dynamics and umbrella sampling, to investigate the thermodynamics of vanillate passing through the pore of OpdK protein at physiological temperature. The results indicate that hydrogen bonds of vanillate-L3 (L3: Gly92-Gln111) and hydrophobic interactions of vanillate-L7 (Gly252-Asn278) are crucial to the transport of vanillate. Compared to L7, L3 can hardly change the shape of the pore, but its amino acids can effectively affect the transport process. The important role of charged residues in the barrel of the protein for the substrate transport has been proved in the experiment researches and our simulations also determinate that these residues may prevent the vanillate from entering the cell. These results provide detailed information that will facilitate the development of effective drugs.

► The transport process of the vanillate was observed via molecular simulations. ► The loops L3 and L7 have great effects in the transport. ► The effect of the bottom charged residues confirmed the experiment researches.