RNA-protein complexes and force field polarizability.

Area of Science:

• Computational chemistry and structural biology
• Biomolecular simulations
• Molecular dynamics of nucleic acid-protein interactions

Background:

• Molecular dynamics (MD) simulations are essential for atomistic studies of biomolecular dynamics.
• Simulations of RNA-protein complexes are less common, highlighting a need for force field evaluation.
• Understanding RNA-protein interactions is vital in molecular biology and drug discovery.

Purpose of the Study:

• To compare the performance of different molecular dynamics force fields in simulating RNA-protein complexes.
• To investigate the impact of polarizability on the stability and dynamics of these complexes.
• To provide guidance on selecting appropriate force fields for RNA-protein simulation studies.

Main Methods:

• Utilized three non-polarizable force fields (Amber ff14SB/ff19SB with OL3, OPLS4) and tested polarizable options (AMOEBA, ff19SB/OL3 with O3P water model).
• Simulated three distinct RNA-protein complexes: Argonaute 2 with RNA, CasPhi-2 with CRISPR RNA, and RIG-I variant with dsRNA.
• Analyzed complex stability, structural integrity, and dynamics under different force field conditions.

Main Results:

• Non-polarizable force fields produced compact and stable RNA-protein complexes.
• Polarizable force fields or water models introduced greater molecular mobility but risked complex structural disintegration, particularly with flexible protein loops.
• All tested force fields demonstrated capability in simulating RNA-protein complexes, with varying degrees of stability and dynamics.

Conclusions:

• The choice of force field significantly influences the outcome of RNA-protein complex simulations.
• Caution is advised when employing polarizable models for long-timescale simulations due to potential instability.
• Optimal force field selection depends on the specific RNA-protein system and the research objectives.