Interplay between Conformational Heterogeneity and Hydration in the Folding Landscape of a Designed Three-Helix Bundle
- Resource Type
- Authors
- Payel Das; Silvina Matysiak; Gregory S. Custer
- Source
- The journal of physical chemistry. B. 121(13)
- Subject
- 0301 basic medicine
Protein Folding
Protein Conformation
Sequence (biology)
Molecular Dynamics Simulation
01 natural sciences
03 medical and health sciences
Molecular dynamics
Protein structure
0103 physical sciences
Materials Chemistry
Folding funnel
Physical and Theoretical Chemistry
Helix bundle
010304 chemical physics
Chemistry
Proteins
Water
Surfaces, Coatings and Films
Folding (chemistry)
Crystallography
030104 developmental biology
Chemical physics
Bundle
Protein folding
Hydrophobic and Hydrophilic Interactions
- Language
- ISSN
- 1520-5207
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.