title: Interplay between Conformational Heterogeneity and Hydration in the Folding Landscape of a Designed Three-Helix Bundle.
abstract: Water is known to play a critical role in protein folding and stability. Here we develop and employ a coarse-grained (CG) model to directly explore the role of water in shaping the conformational landscape explored during protein folding. For this purpose, we simulate a designed sequence with binary patterning of neutral and hydrophobic residues, which is capable of folding to a three-helix bundle in explicit water. We find two folded states of this sequence, with rotation of the helices occurring to trade between hydrophobic packing and water expulsion from the core. This work provides insight into the role of water and hydrophobicity in generating competing folded states for a protein.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Custer
authors.affiliation: IBM Thomas J. Watson Research Center , Yorktown Heights, New York 10598, United States.
authors.forename: Payel
authors.identifier: 0000-0002-7288-0516
authors.initials: P
authors.lastname: Das
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, Maryland 20742, United States.
authors.forename: Silvina
authors.identifier: 0000-0003-3824-9787
authors.initials: S
authors.lastname: Matysiak
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D014867:Water