1 Centre for Research in Molecular Modeling (CERMM) and Department of Chemistry and Biochemistry, Concordia University , 7141 Sherbrooke Street West, Montréal, Québec, Canada H4B 1R6.

Standard molecular dynamics (MD) simulations of gas diffusion consume considerable computational time and resources even for small proteins. To combat this, temperature-controlled locally enhanced sampling (TLES) examines multiple diffusion trajectories per simulation by accommodating multiple noninteracting copies of a gas molecule that diffuse independently, while the protein and water molecules experience an average interaction from all copies. Furthermore, gas migration within a protein...