The entropic cost of protein-protein association: A case study on acetylcholinesterase binding to fasciculin-2

Protein-protein association is accompanied by a large reduction in translational and rotational (external) entropy. Based on a 15 ns molecular dynamics simulation of acetylcholinesterase (AChE) in complex with fasciculin 2 (Fas2), we estimate the loss in external entropy using quasiharmonic analysis and histogram-based approximations of the probability distribution function. The external entropy loss of AChE-Fas2 binding, similar to 30 cal/mol K, is found to be significantly larger than most previously characterized protein-ligand systems. However, it is less than the entropy loss estimated in an earlier study by A.V. Finkelstein and J. Janin, which was based on atomic motions in crystals.