Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition
2022-02-28
Darren Demapan, Jörg Kussmann, Christian Ochsenfeld, and Qiang Cui
J. Chem. Theory Comput., 18, 4, 2530–2542, 2022
To analyze the impact of various technical details on the results of quantum mechanical (QM)/molecular mechanical (MM) enzyme simulations, including the QM region size, catechol-O-methyltransferase (COMT) is studied as a model system using an approximate QM/MM method (DFTB3/CHARMM). The results show that key equilibrium and kinetic properties for methyl transfer in COMT exhibit limited variations with respect to the size of the QM region, which ranges from ∼100 to ∼500 atoms in this study. With extensive sampling, local and global structural characteristics of the enzyme are largely conserved across the studied QM regions, while the nature of the transition state (e.g., secondary kinetic isotope effect) and reaction exergonicity are largely maintained. Deviations in the free energy profile with different QM region sizes are similar in magnitude to those observed with changes in other simulation protocols, such as different initial enzyme conformations and boundary conditions. Electronic structural properties, such as the covariance matrix of residual charge fluctuations, appear to exhibit rather long-range correlations, especially when the peptide backbone is included in the QM region; this observation holds when a range-separated DFT approach is used as the QM region, suggesting that delocalization error is unlikely the origin. Overall, the analyses suggest that multiple simulation details determine the results of QM/MM enzyme simulations with comparable contributions.
Speaker: Prof. Dr. Thomas Carell
Ludwig-Maximilians-Universität München
Institut für Chemische Epigenetik (ICEM)
Department of Chemistry
Office:
Würmtalstrasse 201
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77750
Fax: +49 (0)89 2180-77756
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Management: Dr. Nada Raddaoui
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 03.004
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77755
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Secretary: Birgit Carell
Institute for Chemical Epigenetics Munich (ICEM)
Office:
Würmtalstrasse 201, Building L, Room 00.007
81377 Munich
Germany
Mailing address:
Butenandtstr. 5 - 13
81377 Munich
Germany
Phone: +49 (0)89 2180-77751
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
website support: Martina Schuster
Prof. Dr. Lena Daumann
LMU Munich
Department of Chemistry
Butenandtstr. 5 - 13
House D, Room 3.075
81377 Munich, Germany
Phone: +49 89 2180 77486
This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. Sabine Schneider
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77716
This email address is being protected from spambots. You need JavaScript enabled to view it.
Dr. Martin Sumser (Coordinator)
LMU Munich
Institute for Chemical Epigenetics
Butenandtstr. 5 - 13
House L
81377 Munich, Germany
Phone: +49 89 2180 77765
This email address is being protected from spambots. You need JavaScript enabled to view it.
Contact IRTG 1309 related
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.