Self-Consistent Parameterization of DNA Residues for the Non-Polarizable AMBER Force Fields

Area of Science:

• Computational chemistry
• Molecular dynamics
• Biophysics

Background:

• Fixed-charge force fields are essential for simulating DNA dynamics.
• Accurate parameterization of new residues is crucial for expanding force field utility.
• Atomic charge derivation requires self-consistency with existing force field parameters.

Purpose of the Study:

• To identify optimal structural models for deriving self-consistent atomic charges for nucleic acid force fields.
• To present a contemporary protocol for charge derivation.
• To provide optimized charges for nine non-canonical DNA residues.

Main Methods:

• Benchmarking quantum mechanical models against molecular mechanics (MM) minimization structures for deoxynucleosides.
• Calculating atomic charges by fitting to molecular electrostatic potentials.
• Comparing root-mean-square (RMS) deviation of derived charges against existing AMBER force field values.

Main Results:

• Quantum mechanical models are suboptimal for charge derivation compared to MM minimization structures.
• MM minimization structures yielded charges with up to 6-fold lower RMS deviation.
• A protocol for self-consistent charge derivation and optimized charges for nine non-canonical residues were presented.

Conclusions:

• Molecular mechanics minimization provides superior structural models for atomic charge derivation in DNA force fields.
• The presented protocol and optimized charges facilitate the study of novel DNA polymers.
• Accurate force field parameterization is key to advancing nucleic acid simulations.