What Can Human-Guided Simulations Bring to RNA Folding?

Area of Science:

• Computational Biology
• Biophysics
• Structural Biology

Background:

• Scientific-discovery games have shown promise in predicting molecular structures.
• RNA folding is crucial for biological function and presents a complex computational challenge.

Purpose of the Study:

• To develop and evaluate open-source software for coarse-grained RNA folding simulations guided by human intuition.
• To assess the accuracy of interactive simulations in predicting 3D RNA structures of varying complexity.

Main Methods:

• An interactive experiment involving 141 participants with minimal prior knowledge was conducted.
• Participants used open software for coarse-grained RNA folding simulations.
• Statistical analysis of participant-generated structures and trajectories was compared with replica exchange molecular dynamics simulations.

Main Results:

• Participants rapidly acquired the ability to fold simple and complex RNA topologies with minimal computational time.
• Interactive simulations showed higher success rates when users explored a wider conformational space.
• On-the-fly feedback on root mean square deviation did not enhance model quality.

Conclusions:

• Human-guided simulations offer a viable and efficient approach for RNA folding.
• Interactive RNA folding software can empower users with limited expertise to predict complex structures.
• Exploration of conformational space is key for successful interactive RNA folding.