Selection rules on initial structures in parallel cascade selection molecular dynamics affect conformational sampling...

Area of Science:

• Computational chemistry
• Biophysics
• Molecular dynamics

Background:

• Protein conformational changes are crucial for biological function.
• Accurate simulation of these transitions is computationally challenging.
• Parallel cascade selection molecular dynamics (PaCS-MD) is a method for exploring transition pathways.

Purpose of the Study:

• To investigate the impact of initial structure selection rules on PaCS-MD efficiency.
• To determine the optimal resampling percentage for generating diverse protein transition pathways.
• To reproduce the open-closed transition of di-ubiquitin using PaCS-MD.

Main Methods:

• PaCS-MD simulations were performed with varying resampling percentages (X = 0.1% to 50.0%).
• Root-mean-square deviation (RMSD) from the product state was used as a reaction coordinate.
• The open-closed transition of di-ubiquitin was simulated to evaluate sampling efficiency.

Main Results:

• Different resampling percentages (X) yielded varying conformational sampling efficiencies.
• The broadness of sampled conformational space and the number of cycles required were key metrics.
• Resampling from the top X = 2.0% of configurations showed promising results.

Conclusions:

• The selection rule for initial structures significantly influences PaCS-MD efficiency.
• Resampling from the top approximately 2.0% of highly ranked configurations appears most efficient.
• This optimized approach facilitates the generation of comprehensive transition pathways for proteins.