Sampling activated mechanisms in proteins with the activation-relaxation technique

Area of Science:

• Computational Biology
• Biophysics
• Materials Science

Background:

• Protein dynamics crucial for function occur on millisecond timescales and longer.
• Standard all-atom molecular dynamics simulations are limited to nanosecond timescales, missing key activated mechanisms.
• Advanced simulation methods are necessary to capture slow protein dynamics.

Purpose of the Study:

• To detail the Activation-Relaxation Technique (ART) for generating protein activated mechanisms.
• To demonstrate ART's applicability to all-atom protein simulations.
• To explore protein dynamics beyond the reach of conventional molecular dynamics.

Main Methods:

• The Activation-Relaxation Technique (ART) involves two steps: activation to a saddle point and relaxation to a new minimum.
• ART operates within the configurational energy landscape.
• Simulations utilize an all-atom energy function for a two-helix bundle protein.

Main Results:

• ART successfully generates activated mechanisms relevant to protein dynamics.
• The technique overcomes the timescale limitations of standard molecular dynamics.
• ART has been previously applied to condensed matter systems like metallic glasses and amorphous semiconductors.

Conclusions:

• ART is a powerful method for studying activated processes in proteins.
• This technique enables the observation of crucial long-time protein dynamics.
• ART provides insights into protein mechanisms previously inaccessible through simulations.