# Protein‐spanning water networks and implications for prediction of protein–protein interactions mediated through hydrophobic effects

@article{Cui2014ProteinspanningWN,
title={Protein‐spanning water networks and implications for prediction of protein–protein interactions mediated through hydrophobic effects},
author={Di Cui and Shuching Ou and Sandeep Patel},
journal={Proteins: Structure},
year={2014},
volume={82}
}
• Published 1 December 2014
• Chemistry, Medicine
• Proteins: Structure
Hydrophobic effects, often conflated with hydrophobic forces, are implicated as major determinants in biological association and self‐assembly processes. Protein–protein interactions involved in signaling pathways in living systems are a prime example where hydrophobic effects have profound implications. In the context of protein–protein interactions, a priori knowledge of relevant binding interfaces (i.e., clusters of residues involved directly with binding interactions) is difficult. In the…
22 Citations

## Topics from this paper

Identifying hydrophobic protein patches to inform protein interaction interfaces
• Medicine
Proceedings of the National Academy of Sciences
• 2021
Specialized molecular simulations wherein water molecules are systematically displaced from the protein hydration shell are employed, and it is demonstrated that polar/charged atoms comprise a substantial fraction of hydrophobic protein patches, which establishes a computational framework for characterizing the hydrophobicity of complex solutes, such as proteins, and for uncovering their interaction interfaces.
Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30–35 Chain in Water: A Molecular Dynamics Study
• Chemistry, Biology
• 2016
We study the conformational landscape of the C-terminal fragment of the Amyloid protein Aβ30–35 in water using well-tempered metadynamics simulations and find that it resembles an intrinsically
Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30-35 Chain in Water: A Molecular Dynamics Study.
• Chemistry, Medicine
Journal of chemical information and modeling
• 2017
We have studied the conformational landscape of the C-terminal fragment of the amyloid protein Aβ30-35 in water using well-tempered metadynamics simulations and found that it resembles an
The role of hydrophobic interactions in folding of $\beta$-sheets
The hydrophobic-effect-based mechanism responsible for $\beta$-sheets folding is verified by bioinformatics analyses of thousands of results available from experiments, and the folding codes in amino acid sequence that dictate formation of a $\ beta$-hairpin can be deciphered through evaluating hydrophilic interaction among side-chains of an unfolded polypeptide from a thermodynamic metastable state.
Protein Hydration Waters Are Susceptible to Unfavorable Perturbations.
• Physics, Chemistry
Journal of the American Chemical Society
• 2019
It is found that, akin to extended hydrophobic surfaces, proteins situate their hydration waters at the edge of a dewetting transition, making them susceptible to unfavorable perturbations.
The Role of Interfacial Water in Protein-Ligand Binding: Insights from the Indirect Solvent Mediated Potential of Mean Force.
• Chemistry, Medicine
Journal of chemical theory and computation
• 2018
It is shown that interfacial water locations that contribute favorably or unfavorably at the 1-body level to the solvation free energy of the solute can be targeted as part of the ligand design process.
Entropy-Enthalpy Compensations Fold Proteins in Precise Ways
• Jiacheng Li, +8 authors Xiaodong He
• Medicine
International journal of molecular sciences
• 2021
Protein folding is guided by multistage entropy-enthalpy compensations of the system of polypeptide chains and water molecules under the solution conditions, which is verified by bioinformatics analyses of a dozen structures of dimers.
Spatially Heterogeneous Surface Water Diffusivity around Structured Protein Surfaces at Equilibrium.
• Chemistry, Medicine
Journal of the American Chemical Society
• 2017
This study employs Overhauser dynamic nuclear polarization (ODNP) to probe the equilibrium hydration water dynamics at select sites on the surface of Chemotaxis Y (CheY) in dilute solution and finds DW dynamics to be highly heterogeneous across thesurface of CheY.
Experimental and computational surface hydrophobicity analysis of a non-enveloped virus and proteins.
• Chemistry, Medicine
Colloids and surfaces. B, Biointerfaces
• 2017
It is experimentally and computationally demonstrated that a non-enveloped virus is more hydrophobic than a panel of model proteins used in this study.
Conformational transition of Aβ42 inhibited by a mimetic peptide. A molecular modeling study using QM/MM calculations and QTAIM analysis
Abstract The main pathogenic event in Alzheimer’s disease is believed to be the aggregation of the amyloid β-peptides into toxic aggregates. In a previous work we designed a mimetic peptide

## References

SHOWING 1-10 OF 77 REFERENCES
Free energetics of rigid body association of ubiquitin binding domains: A biochemical model for binding mediated by hydrophobic interaction
• Chemistry, Medicine
Proteins
• 2014
This work uses atomistic molecular dynamics simulations in conjunction with the Adaptive Biasing Force sampling method to compute potentials of mean force (the reversible work, or free energy, associated with the binding process) to investigate the thermodynamic signature of complexation in this well‐studied biochemical model of hydrophobic association and observes that association is favored by entropic contributions from release of water from the interprotein regions.
Water and proteins: a love-hate relationship.
• Chemistry, Medicine
Proceedings of the National Academy of Sciences of the United States of America
• 2004
A significant improvement inprotein structure prediction is reported by adding a water knowledge-based potential to an established Hamiltonian for protein structure prediction, which improves the predicted structures, especially for large proteins, when long-range interactions between polar or charged groups are mediated by water molecules.
A role for surface hydrophobicity in protein‐protein recognition
• Chemistry, Medicine
Protein science : a publication of the Protein Society
• 1994
Results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand, and may be useful for identifying small sets of well‐defined loci for possible ligand attachment.
Thermodynamic analysis of water molecules at the surface of proteins and applications to binding site prediction and characterization
• Chemistry, Medicine
Proteins
• 2012
This work characterize the FKBP12 protein and shows that water molecules observed in crystal structures are less stable on average than bulk water as a consequence of the high degree of spatial localization, thereby resulting in a significant loss in entropy.
Similar binding sites and different partners: implications to shared proteins in cellular pathways.
• Biology, Medicine
Structure
• 2007
It is found that proteins with common binding-site motifs preferentially use conserved interactions at similar interface locations, despite the different partners.
Hot spots—A review of the protein–protein interface determinant amino‐acid residues
• Chemistry, Medicine
Proteins
• 2007
The scope of this review is to summarize all the available information regarding hot spots for a better atomic understanding of their structure and function, to improve the rational design of complexes of high affinity and specificity as well as that of small molecules, which can mimic the functional epitopes of the proteic complexes.
Which properties of a spanning network of hydration water enable biological functions?
• Chemistry, Medicine
Chemphyschem : a European journal of chemical physics and physical chemistry
• 2008
The comparative studies of the various properties of hydrated biosystems in the presence and in the absence of a spanning water network should clarify its specific physical properties, which are crucial for biological functions.
Hydrophobicity of proteins and interfaces: insights from density fluctuations.
• Chemistry, Medicine
Annual review of chemical and biomolecular engineering
• 2011
The ability to include information about hydration water in mapping hydrophobicity is expected to significantly impact the understanding of protein-protein interactions as well as improve drug design and discovery methods and bioseparation processes.
Ion-Specific Induced Fluctuations and Free Energetics of Aqueous Protein Hydrophobic Interfaces: Toward Connecting to Specific-Ion Behaviors at Aqueous Liquid–Vapor Interfaces
• Chemistry, Medicine
The journal of physical chemistry. B
• 2014
This work focuses on fluctuations of an interface between water and a hydrophobic region of hydrophobin-II, a 71 amino acid residue protein expressed by filamentous fungi and known for its ability to form hydrophobically mediated self-assemblies at interfaces such as a water/air interface.
Hydrophobicity of protein surfaces: Separating geometry from chemistry
• Chemistry, Medicine
Proceedings of the National Academy of Sciences
• 2008
This work studies via molecular dynamics simulation the structure and thermodynamics of water confined between two protein-like surfaces, and finds that solvent evacuation of the hydrophobic gap (cavitation) between dimers is observed when the gap has closed to sterically permit a single water layer.