Fragment molecular orbital (FMO) method for studying actinide/lanthanide interaction with DNA/protein


Fragment molecular orbital (FMO) method for studying actinide/lanthanide interaction with DNA/protein

Tsushima, S.; Mochizuki, Y.; Fahmy, K.

Due to its potential health and environmental impacts, actinide binding to biomolecules has been a subject of intensive investigations. A large number of experimental works have been carried out but our understanding remains mostly in a macroscopic scale. Modeling actinide interaction with large biomolecules using ab initio quantum chemical calculations may drastically expand our molecular level knowledge but is challenged by a demand for huge computational resources.
Our strategy to overcome this difficulty is to apply fragment molecular orbital (FMO) method. In FMO, the molecular system of interest is partitioned into small fragments. Each fragment and fragment pair is subject to self-consistent field calculations under environmental electrostatic potentials and the electronic structure of the whole system is reconstituted [1]. This procedure drastically reduces computational cost of Hartree Fock calculations from N3 to N2 (or less) and is readily parallelizable. FMO has been extended to MP2 and to DFT to include electron correlation and was successfully applied to the systems such as hydrated DNA [2].
Currently we are upgrading the FMO program Abinit-MP [3] to implement 5f elements into the program. We first choose uranyl-bound DNA for a case study. Calculations are performed as follows. UO22+-bound d(CGCGAATTCGCG)2 (Dickerson-Drew dodecamer) with 20 Na+ ions and SPC/E water shell with 10 Å thickness is first thermally equilibrated and subsequently submitted to MD simulation at 300 K for 100 ns interval using AMBER 14 program. Force field parameters for UO22+ and coordinating water are those developed by Pomogaev et al. [4]. At each 1 ns time step of MD simulation, the structure is extracted and submitted to FMO single point energy calculation at the MP2 level. In FMO, nucleic unit is appropriately divided into sugar, base, and phosphate fragments. Inter-fragment interaction energy analysis is performed to explore the binding affinity of uranyl to DNA and its influence on base pairing.
[1] K.Kitaura et al. (1999) Chem. Phys. Lett. 313, 701–706.
[2] K.Fukuzawa et al. (2015) Comput.Theor.Chem. 1054, 29–37.
[3] S.Tanaka et al. (2014) Phys. Chem. Chem. Phys. 16, 10310–10344.
[4] V.Pomogaev et al. (2013) Phys. Chem. Chem. Phys. 15, 15954–15963.

  • Poster
    Joint 12th EBSA and 10th ICBP-IUPAP Biophysics Congress, 20.-24.07.2019, Madrid, Spain

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