Reactive simulation methods in biological systems with NAMD and xtb

Kedziora, Gary (PET)

Guo, Hao-Bo
Perminov, Alexander
Bekele, Selemon
Huntington, Baxter
Hinkle, Kevin
Berry, Rajiv

Advanced Materials Development

Mixed molecular mechanics (MM) and quantum mechanics (QM) methods (QM/MM) have been used for modeling reactions in biological systems for several years. For example, the popular highperformance classical molecular dynamics code NAMD has the ability to interface with QM codes using a scripting interface and has built in interfaces for MOLPAC and ORCA. The semi-empirical based MOLPAC, while relatively fast, is not parallelized. ORCA is feature rich, supporting both semi-empirical methods and density functional theory. However, ORCA does not license DoD researchers. Scripts to combine a thread-parallelized code xtb with NAMD were developed and example workflows were implemented. The xtb code implements the tight-binding semi-empirical method, GNF2-xTB, which has reliable coverage of all atoms of the periodic table through Radon. The combination of NAMD with xtb opens the possibility for simulations of a wide range of reactions in biological systems including those with exotic elements. Performance of the method will be demonstrated using the example of the free energy on the reaction path in a decarboxylase enzyme.