Molecular Dynamics of Apo-Adenylate Kinase: A Distance Replica Exchange Method for the Free Energy of Conformational Fluctuations

• DOI: 10.1021/jp064303c
• Publication Date: 2006-11-07T12:01:13Z
• Authors: Hongfeng Lou; Robert I. Cukier
• Keywords: Reaction coordinate; Umbrella sampling

A large domain motion in adenylate kinase from E. coli (AKE) is studied with molecular dynamics. AKE undergoes a large-scale rearrangement of its lid and AMP-binding domains when the open form closes over substrates, AMP, Mg2+-ATP, whereby come closer to core. The third domain, core, relatively stable during this motion. reaction coordinate that monitors distance between core selected be able compare results energy transfer experiments. Sampling along carried out by using replica exchange method (DREM), where systems differ restraint potential enforcing different values are independently simulated periodic attempts at these systems. Several methods used study efficiency convergence properties DREM simulation compared an analogous non-DREM simulation. greatly accelerates rate extent configurational sampling leads equilibrium as measured monitoring collective modes obtained principal analysis. mean force reveals rather flat region for distances closed conformation. smaller has distinct minimum quite close found X-ray structure. In concert decrease (AMP-binding-to-core distance) lid-to-core also decreases. Therefore, apo can fluctuate conformations similar structure, even absence substrates.