Sampling small-scale and large-scale conformational changes in proteins and molecular complexes

Area of Science:

• Computational Biology
• Biophysics
• Molecular Dynamics

Background:

• Accurate sampling of molecular motions is vital for computational studies like protein-protein docking and ligand binding.
• Existing methods may face challenges in capturing large-scale conformational changes in complex biological systems.

Purpose of the Study:

• To report the further development and application of the activation-relaxation technique for internal coordinate space trajectories (ARTIST).
• To demonstrate ARTIST's capability in generating complex and large conformational moves for proteins and protein complexes.

Main Methods:

• Utilizing the activation-relaxation technique to identify and cross saddle points connecting energy minima.
• Applying ARTIST to simulate conformational changes in all-atom protein systems and protein complexes.

Main Results:

• ARTIST successfully generated conformational moves of various complexities and sizes.
• Simulations included two all-atom proteins and three protein complexes (70-300 amino acids).
• The method proved effective in dense systems like protein-protein complexes.

Conclusions:

• ARTIST facilitates the comprehensive sampling of all degrees of freedom in dense biological systems.
• This technique advances the computational treatment of protein dynamics, particularly in complex interactions.
• ARTIST offers a powerful approach for studying protein-protein docking and ligand binding.