Ligand Diffusion on Protein Surface Observed in Molecular Dynamics Simulation.
The process of binding of small ligands to dihydrofolate reductase protein has been investigated using all-atom molecular dynamics simulations. The existence of a mechanism that facilitates the search of the binding site by the ligand is demonstrated. The mechanism consists of ligand diffusing on the protein's surface. It has been discussed in the literature before, but has not been explicitly confirmed for realistic molecular systems. The strength of this nonspecific binding is roughly estimated and found to be essential for the binding kinetics.
†Nonlinearity and Complexity Research Group, Aston University, Birmingham, B4 7ET, U.K.
Dmitry
D
Nerukh
‡RIKEN Advanced Institute for Computational Science, 7-1-26, Minatojima-minami-machi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Noriaki
N
Okimoto
Atsushi
A
Suenaga
‡RIKEN Advanced Institute for Computational Science, 7-1-26, Minatojima-minami-machi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Makoto
M
Taiji
Mycobacterium tuberculosis dihydrofolate reductase; binding rate; facilitated binding; protein ligand binding; small ligand binding; surface diffusion