Hydration effects on enzyme–substrate complex of nylon oligomer hydrolase: inter-fragment interaction energy study by the fragment molecular orbital method

Abstract

Fragment molecular orbital calculations were successfully applied to a nylon oligomer hydrolase, NylB, to investigate the hydration effects on an enzyme–substrate binding structure. Statistically corrected inter-fragment interaction energy analyses were performed on this system to quantitatively characterise the interactions between the substrate, 6-aminohexanoate linear dimer (ALD), and the amino acid residues, such as Asp181, Ser112, and Ile 345, which are regarded as important for enzyme–substrate complex formation by NylB. We found that the direct interaction between ALD and NylB is weakened by hydration, because water molecules cause charge translation or polarisation of ALD or each amino acid residue. However, including the interaction energy between ALD and water molecules greatly stabilises this complex. These results indicate the importance of the hydration effects in enzyme–substrate complex formation.

Keywords:

• enzyme
• fragment molecular orbital (FMO) method
• inter-fragment interaction energy (IFIE) analysis
• statistically corrected inter-fragment interaction energy (SCIFIE) analysis
• hydration effects

Acknowledgements

FMO calculations were performed using cluster computers at Rikkyo University, Japan.

Additional information

Funding

This study is supported by a Fellowship for the doctor course students [KAKENHI No. 253029] from the Japan Society for the Promotion of Science (JSPS). This is also partly supported by a Grant-in-Aid for Young Scientists (A) [KAKENHI No. 22685003] from JSPS, by a Grant-in-Aid for the innovative area ‘Computics’ and ‘Dynamic ordering of biomolecular systems for creation of integrated systems’ [KAKENHI No. 25104716], [KAKENHI No. 26102525] from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and by the Center for Research on Innovative Simulation Software (CISS) at the Institute of Industrial Science (IIS) of the University of Tokyo.