Parameter optimized surfaces (POPS): analysis of key interactions and conformational changes in the ribosome

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• Calculating solvent accessible surface area (SASA) is crucial for understanding molecular interactions.
• Existing methods can be computationally intensive, limiting their application in large-scale simulations.

Purpose of the Study:

• Introduce Parameter Optimized Surfaces (POPS-A and POPS-R), novel methods for calculating atomic and residue-level SASA.
• Optimize an analytical formula for fast and accurate SASA approximation, suitable for molecular dynamics.
• Apply POPS-R to analyze large macromolecular assemblies, such as ribosomes, and refine low-resolution structures.

Main Methods:

• Developed Parameter Optimized Surfaces (POPS-A and POPS-R) for atomic and residue-level SASA calculations.
• Optimized an analytical formula for approximating solvent accessibilities, focusing on speed and simplicity.
• Applied POPS-R to analyze the structures of 70S, 50S, and 30S ribosomes, identifying subunit interactions.

Main Results:

• POPS provides a computationally efficient method for SASA calculation.
• Analysis of ribosome structures revealed subunit interactions and differences between 30S alone and within the 70S complex.
• Identified conformational rearrangements in the 70S ribosome upon P-tRNA binding, exposing specific amino acid residues.

Conclusions:

• POPS is a practical tool for molecular dynamics simulations and analysis of large macromolecular assemblies.
• POPS-R is effective for refining low-resolution structures and understanding interactions within ribosomes.
• POPS-R facilitates estimation of free energy loss upon complex formation, aiding in the design of protein-RNA complexes.