All-atom polarizable force field for DNA based on the classical Drude oscillator model

Area of Science:

• Computational Chemistry
• Molecular Dynamics
• Biophysics

Background:

• Accurate molecular dynamics simulations require force fields that capture electronic polarization.
• Existing additive force fields often struggle to represent the dynamic response of DNA to its environment.

Purpose of the Study:

• To develop and validate a first-generation atomistic force field for DNA incorporating electronic polarization.
• To improve the simulation accuracy of DNA structural dynamics and properties.

Main Methods:

• Utilized the classical Drude oscillator formalism to model electronic polarization.
• Parameterized the force field using quantum mechanical data for small molecules and experimental DNA properties.
• Performed molecular dynamics simulations of DNA duplexes up to 100 ns.

Main Results:

• The developed Drude force field produced stable DNA duplexes.
• Successfully reproduced the equilibrium between DNA A and B forms.
• Accurately captured transitions between B-DNA substates (BI and BII).
• Showed improved gas-phase quantum mechanical property reproduction compared to CHARMM36.
• Observed larger and more dynamic base dipole moments and perturbed water dipoles in DNA grooves.

Conclusions:

• The Drude force field offers a more physically realistic representation of DNA by including polarizability.
• This model enhances the simulation of DNA conformational dynamics and environmental interactions.
• The improved accuracy holds promise for future studies of DNA behavior in biological systems.