Optimum QM Size for Converged Energy and Free Energy Profiles in QM/MM Simulations

Susanta Das susanta.das@biu.ac.il 1 Kwangho Nam 2,3 Dan Thomas Major 1
1Department of Chemistry, Bar – Ilan University, Ramat-Gan 52900, Israel
2Department of Chemistry, Umeå University, 901 87 Umeå, Sweden
3Department of Chemistry and Biochemistry, University of Texas at Arlington, TX 76019-0065, Arlington, USA

In the current study, we focus on the convergence of energy and free energy reaction profiles with QM size in QM/MM simulations using a proton transfer in a DNA base pair as a test case.1 The QM region is treated with the AM1d/-Phot Hamiltonian, which was developed to accurately describe phosphoryl and proton transfer reactions, in conjunction with an electrostatic embedding scheme using the particle-mesh Ewald summation method.2 Applying this QM/MM potential, we perform extensive sampling, and our result shown that the energy, as well as free energy, reaction profiles converge rapidly to within ±2 kcal/mol with only 30 atoms in the QM region. This finding suggests that the strategy of QM/MM simulations with reasonably sized QM regions, which has been employed for over four decades, still provides a practical approach for modeling complex biomolecular system.3-5

Single proton transfer in DNA

References:

  1. Rossbach, S.; Ochsenfeld, C., Influence of Coupling and Embedding Schemes on QM Size Convergence in QM/MM Approaches for the Example of a Proton Transfer in DNA. J Chem Theory Comput 2017, 13 (3), 1102-1107.
  2. Nam, K.; Cui, Q.; Gao, J.; York, D. M., Specific Reaction Parametrization of the AM1/d Hamiltonian for Phosphoryl Transfer Reactions: H, O, and P Atoms. J Chem Theory Comput 2007, 3 (2), 486-504.
  3. Jindal, G.; Warshel, A., Exploring the Dependence of QM/MM Calculations of Enzyme Catalysis on the Size of the QM Region. J Phys Chem B 2016, 120 (37), 9913-9921.
  4. Major, D. T., Electrostatic Control of Chemistry in Terpene Cyclases. Acs Catal 2017, 7 (8), 5461-5465.
  5. Freud, Y.; Ansbacher, T.; Major, D. T., Catalytic Control in the Facile Proton Transfer in Taxadiene Synthase. Acs Catal 2017, 7 (11), 7653-7657.








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