Drying and hydrophobic collapse in the multi-domain protein and protein oligomers

COMP 224

Xuhui Huang, xhuang@chem.columbia.edu1, Ruhong Zhou, ruhongz@us.ibm.com2, Pu Liu, puliu@chem.columbia.edu1, Claudio J. Margulis, claudio-margulis@uiowa.edu3, and BJ. Berne, berne@chem.columbia.edu1. (1) Department of Chemistry, Columbia University, 3000 Brodaway, New York, NY 10027, (2) Computational Biology Center, IBM TJ Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, NY 10598, (3) Department of Chemistry, University of Iowa, Iowa City, IA 52242
The existence of a drying transition for water confined between hydrophobic particles was found to be sensitive to the solute-solvent attractions in molecular dynamics simulations. A drying phenomenon was observed between two paraffin-like plates, but not between two graphite plates. What happens in protein collapse? In the folding of a multi-domain protein, BphC enzyme, no drying transition was observed even at very small inter-domain distances. For example, liquid water persisted with a density only 10 to 15% lower than in the bulk at 4 Angstrom separation of the domains. However, when the attractive forces between protein and water were turned off, a dewetting transition occurred in the inter-domain region and the collapse of the two domains sped up by more than an order of magnitude. On the other hand, the melittin tetramer, displayed a surprising drying transition inside the nanoscale channel formed by the tetramer. To our knowledge, this is the first time a drying transition was found in real protein systems. Surface topology can have significant effects on the drying transition of this system. Single point mutations of the isoleucines in certain locations can switch the channel from being dry to being wet. Study of the collapse dynamics showed that this hydrophobic collapse was induced by a drying transition in a fraction of the trajectories.