Chem-Bio Informatics Journal
Online ISSN : 1347-0442
Print ISSN : 1347-6297
ISSN-L : 1347-0442
Current issue
Displaying 1-2 of 2 articles from this issue
opinion
  • Hiroshi Iijima
    Article type: opinion
    Subject area: In silico drug discovery
    2024 Volume 24 Pages 1-12
    Published: February 13, 2024
    Released on J-STAGE: February 13, 2024
    JOURNAL FREE ACCESS

    Enzyme kinetics is widely used in many biological studies. Most of enzyme kinetic formulae are derived based on the steady state assumption, which is mathematically expressed by a time- differential equation, namely, d(an enzyme state)/dt = 0 in conventional textbooks. In this opinion article, I would like to propose flux method for handling the steady state assumption.In the proposed flux method, a steady state is defined as the condition wherein the flux entering to the state is equal to the flux leaving that state, implying that the traffic of materials passing through the state is nonzero. How the concept of flux, a type of flow rate, is useful for understanding the nature of enzyme reactions and enzyme kinetic studies will be discussed.

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calculation report
  • Yuya Seki, Chiduru Watanabe, Norihiko Tani, Kikuko Kamisaka, Tatsuya O ...
    Article type: calculation report
    Subject area: Molecular recognition and molecular modeling
    2024 Volume 24 Pages 13-24
    Published: May 17, 2024
    Released on J-STAGE: May 17, 2024
    JOURNAL FREE ACCESS
    Supplementary material

    In modeling structures with multiple conformers, the one with the higher occupancy is typically used under implicit understanding. Multiple conformers have rarely been studied to determine whether a structure with a higher ligand occupancy conformer is more stable and has stronger protein-ligand binding than the one with the lower occupancy. We performed fragment molecular orbital (FMO) calculations on complexes with high and low ligand occupancies, comparing their energies, such as total energy and ligand binding energy, to investigate this question. The structures for FMO calculation were the SARS-CoV-2 main protease (Mpro) and the covalent inhibitor, GC376. The initial X-ray crystal structure of the complex (PDB ID: 7CB7) possessed stereo isomers of GC376, namely B1S (R form) and K36 (S form), with different occupancies. Our findings showed that for all structural optimization conditions, the total energy of the high ligand occupancy B1S complex was lower than that of the low ligand occupancy K36 complex. In addition, stronger interfragment interaction energy (IFIE) of B1S than of K36 was confirmed for most structural optimization conditions. These differences between B1S and K36 are caused by the presence and absence of a hydrogen bond between the ligand and His41, as revealed by IFIE and structural geometry analyses between the ligand and each amino acid residue of Mpro. The present study, under several structural optimization conditions, would have the potential to model energetically stable structures by efficiently selecting high occupancy conformers from structures with different ones.

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