The implementation of a fast and accurate QM/MM potential method in Amber

Abstract

Version 9 of the Amber simulation programs includes a new semi-empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many nanoseconds. The link atom approach used for treating the QM/MM boundary shows improved performance, and the user interface has been rewritten to bring the format into line with classical MD simulations. Support is provided for the PM3, PDDG/PM3, PM3CARB1, AM1, MNDO, and PDDG/MNDO semi-empirical Hamiltonians as well as the self-consistent charge density functional tight binding (SCC-DFTB) method. Performance has been improved to the point where using QM/MM, for a QM system of 71 atoms within an explicitly solvated protein using periodic boundaries and PME requires less than twice the cpu time of the corresponding classical simulation.

Implementation of the SCC-DFTB Method for Hybrid QM/MM Simulations within the Amber Molecular Dynamics Package

“…Test calculations have shown that this approach gives significantly better stability of the charge on QM atoms around the QM-MM interface than is observed if the QM link atom interacts only with other QM atoms not seeing the MM charge field. 26 In addition while our link atom approach introduces a slight displacement in position of the charge on the MM link atom to a dynamic charge on the link atom the overall effect is likely to be very minor. Also, the gradients are formally correctly dealt with when transferring the force on the QM link atom back to the atoms making up the QM-MM link pair and so this approach properly conserves energy.…”

“…For DFTB calculations we use a link atom scheme developed as part of the re-writing of AMBER's semi-empirical QM/MM method is used. 26 This approach is similar to that used by Dynamo, 36 where the link atom is treated as part of the covalent bond between the QM and MM atoms bonded across the interface. Each time an energy or gradient calculation is to be done the link atom coordinates are automatically generated from the current coordinates of the QM and MM atoms making up the QM-MM covalent pair.…”

“…For this a number of approaches was investigated. 26 The best method found is one where all electrostatic interactions between any MM atom (excluding MM atoms directly bonded to a QM atom) that is within the user specified cut-off distance of any QM atom are calculated for all QM atoms, including the link atom, without exclusion or scaling. This method overestimates the interactions of 1-2, 1-3 and 1-4 QM/MM atom pairs due to the fact that these interactions are included in the bond, angle and dihedral parameterization and in the QM calculation.…”

“…However, while not always the optimum method it is simple to implement and experience has shown that it behaves well in the widest variety of situations. 26 Charge conservation with link atoms is achieved by one of two methods. Any difference in charge between the QM region and the parameterized charges of the MM atoms that are replaced by QM atoms can either be distributed to the MM atoms surrounding the MM link atom pair or evenly across all the remaining MM atoms.…”

“…24,25 This manuscript refers specifically to the implementation of the SCC-DFTB method in AMBER, while the implementation of the other QM methods along with support for Generalized Born and the development of a QM/ MM compatible Particle Mesh Ewald treatment of long range electrostatics are discussed in a separate article. 26 …”