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Potential of Mean Force and Umbrella Sampling Simulation for the Transport of 5-Oxazolidinone in Heterotetrameric Sarcosine Oxidase
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  • Shigetaka YonedaOrcid,
  • Takami Saito,
  • Daisuke Nakajima,
  • Go Watanabe
Shigetaka Yoneda
Orcid
Kitasato University - Sagamihara Campus
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Takami Saito
Kitasato University - Sagamihara Campus
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Daisuke Nakajima
Kitasato University - Sagamihara Campus
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Go Watanabe
Kitasato University - Sagamihara Campus
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Peer review status:UNDER REVIEW

21 May 2020Submitted to PROTEINS: Structure, Function, and Bioinformatics
22 May 2020Assigned to Editor
22 May 2020Submission Checks Completed
13 Jun 2020Reviewer(s) Assigned
02 Aug 2020Review(s) Completed, Editorial Evaluation Pending

Abstract

The structure of heterotetrameric sarcosine oxidase (HSO) contains a highly complex system composed of a large cavity and tunnels, which are essential for the reaction and migration of the reactants, products, and intermediates. Previous molecular dynamics (MD) simulation of HSO has identified the regions containing the water channels from the density distribution of water. The simulation is consistent with the selective transport hypothesis of the migration of the iminium intermediate, 5-oxazolidinone (5-OXA), of the enzyme reaction whereby tunnel T3 is the exit pathway of 5-OXA. In the present study, the potential of mean force (PMF) for the transport of 5-OXA through tunnels T1, T2, and T3 was calculated using umbrella sampling (US) MD simulations and the weighted histogram analysis method. The maximum errors of the calculated PMF were estimated by repeating the US simulations using different sets of initial positions. The PMF profiles for the three tunnels support the notion that tunnel T3 is the exit pathway of 5-OXA and that 5-OXA tends to stay at the middle of the tunnel. The PMF profile for the transport of glycine through tunnel T3 was also calculated to investigate where 5-OXA is converted into glycine, and how glycine is released to the outside of HSO was explained.