van der Waals Parameter Scanning with Amber Nucleic Acid Force Fields: Revisiting Means to Better Capture the RNA/DNA...

Area of Science:

• Biophysics
• Computational Chemistry
• Structural Biology

Background:

• Molecular dynamics (MD) simulations are crucial for understanding biomolecular interactions.
• Noncanonical nucleic acid structures present simulation challenges due to force field deficiencies, particularly in van der Waals (vdW) parameter handling.
• Existing vdW parameters in common force fields have not been updated with modern simulation methods.

Purpose of the Study:

• To investigate the impact of subtle van der Waals (vdW) radii modifications on simulating nucleic acid structures.
• To assess the efficacy of vdW parameter adjustments in improving the accuracy of molecular dynamics simulations for RNA and DNA.
• To provide insights for future force field development in nucleic acid simulations.

Main Methods:

• Utilized multidimensional replica exchange molecular dynamics (M-REMD) simulations.
• Applied minute shifts to van der Waals (vdW) radii within commonly used Amber force fields.
• Tested adjustments on RNA tetranucleotide (GACC), B-DNA, and Z-DNA model systems.

Main Results:

• Scanning O2' vdW radii in the GACC RNA tetranucleotide shifted structural distribution between NMR minor and anomalous populations.
• B-DNA structures showed minimal changes, while Z-DNA descriptions improved significantly with vdW adjustments (LJbb) and CUFIX modifications, particularly with the Tumuc1 force field.
• No significant impact on the NMR Major conformation population of the GACC RNA tetranucleotide was observed.

Conclusions:

• Subtle vdW radii modifications can influence specific nucleic acid structural populations in simulations.
• vdW parameter adjustments, alongside other modifications like CUFIX, show promise for improving Z-DNA simulations.
• While not a universal solution, these findings offer valuable direction for refining nucleic acid force fields in computational studies.