Brownian dynamics simulations of aldolase binding glyceraldehyde 3-phosphate dehydrogenase and the possibility of substrate channeling

Brownian dynamics (BD) simulations test for channeling of the substrate, gl yceraldehyde 3-phosphate (GAP), as it passes between the enzymes fructose-1 ,6-bisphosphate aldolase (aldolase) and glyceraldehyde 3-phosphate dehydrog enase (GAPDH). First, ED simulations determined the favorable complexes bet ween aldolase and GAPDH; two adjacent subunits of GAPDH form salt bridges w ith two subunits of aldolase. These intermolecular contacts provide a stron g electrostatic interaction between the enzymes. Second, ED simulates GAP m oving out of the active site of the A or D aldolase subunit and entering an y of the four active sites of GAPDH. The efficiency of transfer is determin ed as the relative number of ED trajectories that reached any active site o f GAPDH. The distribution functions of the transfer time were calculated ba sed on the duration of successful trajectories. ED simulations of the GAP b inding from solution to aldolase/GAPDH complex were compared to the channel ing simulations. The efficiency of transfer of GAP within an aldolase/GAPDH complex was 2 to 3% compared to 1.3% when GAP was binding to GAPDH from so lution. There is a preference for GAP channeling between aldolase and GAPDH when compared to binding from solution. However, this preference is not la rge enough to be considered as a theoretical proof of channeling between th ese proteins.