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Title: Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides

Abstract

We report on the solvation free energy of two different conformations (helix and extended) of two different peptides (deca-alanine and deca-glycine) in two different solvents (water and aqueous guanidinium chloride, GdmCl). The free energies are gained using the quasichemical organization of the potential distribution theorem, an approach that naturally provides the repulsive (solvophobic or cavity) and attractive (solvophilic) contributions to solvation. The solvophilic contribution is further parsed into a chemistry contribution arising from solute interaction with the solvent in the first solvation shell and a long-range contribution arising from non-specific interactions between the solute and the solvent beyond the first solvation shell. The cavity contribution is obtained for two different envelopes, Σ SE, which theory helps identify as the solvent excluded volume, and Σ G, a larger envelope beyond which solute-solvent interactions are Gaussian. The Σ SE envelope is independent of the solvent, as expected on the basis of the insensitivity to the solvent type of the distance of closest approach between protein heavy atoms and solvent heavy atoms, but contrary to the intuition based on treating solvent constituents as spheres of some effective radii. For both envelopes, the cavity contribution in water is proportional to the surface area ofmore » the envelope. The same does not hold for GdmCl(aq), revealing the limitation of using molecular area to assess solvation energetics. The Σ G-cavity contribution predicts that GdmCl(aq) should favor the more compact state, contrary to the role of GdmCl in unfolding proteins. The chemistry contribution attenuates this effect, but still the net local (chemistry plus Σ G-packing) contribution is inadequate in capturing the role of GdmCl. With the inclusion of the long-range contribution, which is dominated by van der Waals interaction, aqueous GdmCl favors the extended conformation over the compact conformation. Our result emphasizes the importance of weak, but attractive, long-range dispersion interactions in protein solution thermodynamics.« less

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [2]
  1. Johns Hopkins Univ., Baltimore, MD (United States); Pfizer, St. Louis, MO (United States)
  2. Rice Univ., Houston, TX (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Oakland, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1543855
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Chemical Physics
Additional Journal Information:
Journal Volume: 148; Journal Issue: 22; Journal ID: ISSN 0021-9606
Publisher:
American Institute of Physics (AIP)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Tomar, Dheeraj S., Ramesh, Niral, and Asthagiri, D. Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides. United States: N. p., 2018. Web. doi:10.1063/1.5022465.
Tomar, Dheeraj S., Ramesh, Niral, & Asthagiri, D. Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides. United States. doi:10.1063/1.5022465.
Tomar, Dheeraj S., Ramesh, Niral, and Asthagiri, D. Tue . "Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides". United States. doi:10.1063/1.5022465. https://www.osti.gov/servlets/purl/1543855.
@article{osti_1543855,
title = {Solvophobic and solvophilic contributions in the water-to-aqueous guanidinium chloride transfer free energy of model peptides},
author = {Tomar, Dheeraj S. and Ramesh, Niral and Asthagiri, D.},
abstractNote = {We report on the solvation free energy of two different conformations (helix and extended) of two different peptides (deca-alanine and deca-glycine) in two different solvents (water and aqueous guanidinium chloride, GdmCl). The free energies are gained using the quasichemical organization of the potential distribution theorem, an approach that naturally provides the repulsive (solvophobic or cavity) and attractive (solvophilic) contributions to solvation. The solvophilic contribution is further parsed into a chemistry contribution arising from solute interaction with the solvent in the first solvation shell and a long-range contribution arising from non-specific interactions between the solute and the solvent beyond the first solvation shell. The cavity contribution is obtained for two different envelopes, ΣSE, which theory helps identify as the solvent excluded volume, and ΣG, a larger envelope beyond which solute-solvent interactions are Gaussian. The ΣSE envelope is independent of the solvent, as expected on the basis of the insensitivity to the solvent type of the distance of closest approach between protein heavy atoms and solvent heavy atoms, but contrary to the intuition based on treating solvent constituents as spheres of some effective radii. For both envelopes, the cavity contribution in water is proportional to the surface area of the envelope. The same does not hold for GdmCl(aq), revealing the limitation of using molecular area to assess solvation energetics. The ΣG-cavity contribution predicts that GdmCl(aq) should favor the more compact state, contrary to the role of GdmCl in unfolding proteins. The chemistry contribution attenuates this effect, but still the net local (chemistry plus ΣG-packing) contribution is inadequate in capturing the role of GdmCl. With the inclusion of the long-range contribution, which is dominated by van der Waals interaction, aqueous GdmCl favors the extended conformation over the compact conformation. Our result emphasizes the importance of weak, but attractive, long-range dispersion interactions in protein solution thermodynamics.},
doi = {10.1063/1.5022465},
journal = {Journal of Chemical Physics},
number = 22,
volume = 148,
place = {United States},
year = {2018},
month = {4}
}

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Works referenced in this record:

Hydration Free Energies of Amino Acids: Why Side Chain Analog Data Are Not Enough
journal, July 2009

  • König, Gerhard; Boresch, Stefan
  • The Journal of Physical Chemistry B, Vol. 113, Issue 26
  • DOI: 10.1021/jp902638y

NAMD2: Greater Scalability for Parallel Molecular Dynamics
journal, May 1999

  • Kalé, Laxmikant; Skeel, Robert; Bhandarkar, Milind
  • Journal of Computational Physics, Vol. 151, Issue 1
  • DOI: 10.1006/jcph.1999.6201

Isothermal Unfolding of Globular Proteins in Aqueous Urea Solutions
journal, May 1964

  • Tanford, Charles.
  • Journal of the American Chemical Society, Vol. 86, Issue 10
  • DOI: 10.1021/ja01064a028

Test of the Monte Carlo Method: Fast Simulation of a Small Ising Lattice
journal, June 1970

  • Friedberg, R.; Cameron, J. E.
  • The Journal of Chemical Physics, Vol. 52, Issue 12
  • DOI: 10.1063/1.1672907

Modeling molecular and ionic absolute solvation free energies with quasichemical theory bounds
journal, October 2008

  • Rogers, David M.; Beck, Thomas L.
  • The Journal of Chemical Physics, Vol. 129, Issue 13
  • DOI: 10.1063/1.2985613

Surface tension measurements show that chaotropic salting-in denaturants are not just water-structure breakers.
journal, January 1990

  • Breslow, R.; Guo, T.
  • Proceedings of the National Academy of Sciences, Vol. 87, Issue 1
  • DOI: 10.1073/pnas.87.1.167

Osmolyte effects on protein stability and solubility: A balancing act between backbone and side-chains
journal, November 2011


Urea and Guanidinium Induced Denaturation of a Trp-Cage Miniprotein
journal, July 2011

  • Heyda, Jan; Kožíšek, Milan; Bednárova, Lucie
  • The Journal of Physical Chemistry B, Vol. 115, Issue 28
  • DOI: 10.1021/jp200790h

Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Limited validity of group additivity for the folding energetics of the peptide group
journal, November 2005

  • Avbelj, Franc; Baldwin, Robert L.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 63, Issue 2
  • DOI: 10.1002/prot.20756

Exploring Multidimensional Free Energy Landscapes Using Time-Dependent Biases on Collective Variables
journal, December 2009

  • Hénin, Jérome; Fiorin, Giacomo; Chipot, Christophe
  • Journal of Chemical Theory and Computation, Vol. 6, Issue 1
  • DOI: 10.1021/ct9004432

Peptide Conformational Preferences in Osmolyte Solutions: Transfer Free Energies of Decaalanine
journal, February 2011

  • Kokubo, Hironori; Hu, Char Y.; Pettitt, B. Montgomery
  • Journal of the American Chemical Society, Vol. 133, Issue 6
  • DOI: 10.1021/ja1078128

Are Solvation Free Energies of Homogeneous Helical Peptides Additive?
journal, October 2005

  • Staritzbichler, René; Gu, Wei; Helms, Volkhard
  • The Journal of Physical Chemistry B, Vol. 109, Issue 40
  • DOI: 10.1021/jp052403x

Intramolecular Interactions Overcome Hydration to Drive the Collapse Transition of Gly 15
journal, August 2017

  • Asthagiri, D.; Karandur, Deepti; Tomar, Dheeraj S.
  • The Journal of Physical Chemistry B, Vol. 121, Issue 34
  • DOI: 10.1021/acs.jpcb.7b05469

Unfolding of Hydrophobic Polymers in Guanidinium Chloride Solutions
journal, February 2010

  • Godawat, Rahul; Jamadagni, Sumanth N.; Garde, Shekhar
  • The Journal of Physical Chemistry B, Vol. 114, Issue 6
  • DOI: 10.1021/jp906976q

Potential-distribution theory and the statistical mechanics of fluids
journal, March 1982


Calculation of free‐energy differences from computer simulations of initial and final states
journal, August 1996

  • Hummer, Gerhard; Szabo, Attila
  • The Journal of Chemical Physics, Vol. 105, Issue 5
  • DOI: 10.1063/1.472068

Simulation of activation free energies in molecular systems
journal, August 1996

  • Neria, Eyal; Fischer, Stefan; Karplus, Martin
  • The Journal of Chemical Physics, Vol. 105, Issue 5
  • DOI: 10.1063/1.472061

Comparison of simple potential functions for simulating liquid water
journal, July 1983

  • Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
  • The Journal of Chemical Physics, Vol. 79, Issue 2
  • DOI: 10.1063/1.445869

Communication: Regularizing binding energy distributions and thermodynamics of hydration: Theory and application to water modeled with classical and ab initio simulations
journal, November 2011

  • Weber, Valéry; Merchant, Safir; Asthagiri, D.
  • The Journal of Chemical Physics, Vol. 135, Issue 18
  • DOI: 10.1063/1.3660205

Urea, but not guanidinium, destabilizes proteins by forming hydrogen bonds to the peptide group
journal, February 2009

  • Lim, Woon Ki; Rösgen, Jörg; Englander, S. Walter
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 8
  • DOI: 10.1073/pnas.0812588106

All-Atom Empirical Potential for Molecular Modeling and Dynamics Studies of Proteins
journal, April 1998

  • MacKerell, A. D.; Bashford, D.; Bellott, M.
  • The Journal of Physical Chemistry B, Vol. 102, Issue 18
  • DOI: 10.1021/jp973084f

Contribution of Hydrophobic Interactions to the Stability of the Globular Conformation of Proteins
journal, November 1962

  • Tanford, Charles.
  • Journal of the American Chemical Society, Vol. 84, Issue 22
  • DOI: 10.1021/ja00881a009

Backbone additivity in the transfer model of protein solvation
journal, January 2010

  • Hu, Char Y.; Kokubo, Hironori; Lynch, Gillian C.
  • Protein Science
  • DOI: 10.1002/pro.378

Trimethylamine N -oxide influence on the backbone of proteins: An oligoglycine model
journal, January 2009

  • Hu, Char Y.; Lynch, Gillian C.; Kokubo, Hironori
  • Proteins: Structure, Function, and Bioinformatics
  • DOI: 10.1002/prot.22598

CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields
journal, January 2009

  • Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.
  • Journal of Computational Chemistry
  • DOI: 10.1002/jcc.21367

Quantitative Assessments of the Distinct Contributions of Polypeptide Backbone Amides versus Side Chain Groups to Chain Expansion via Chemical Denaturation
journal, February 2015

  • Holehouse, Alex S.; Garai, Kanchan; Lyle, Nicholas
  • Journal of the American Chemical Society, Vol. 137, Issue 8
  • DOI: 10.1021/ja512062h

Comparison of Guanidine Hydrochloride (GdnHCl) and Urea Denaturation on Inactivation and Unfolding of Human Placental Cystatin (HPC)
journal, July 2005


Conditional Solvation Thermodynamics of Isoleucine in Model Peptides and the Limitations of the Group-Transfer Model
journal, April 2014

  • Tomar, Dheeraj S.; Weber, Valéry; Pettitt, B. Montgomery
  • The Journal of Physical Chemistry B, Vol. 118, Issue 15
  • DOI: 10.1021/jp500727u

Additivity Principles in Biochemistry
journal, January 1997


A Kirkwood-Buff derived force field for the simulation of aqueous guanidinium chloride solutions
journal, August 2004

  • Weerasinghe, Samantha; Smith, Paul E.
  • The Journal of Chemical Physics, Vol. 121, Issue 5
  • DOI: 10.1063/1.1768938

Regularizing Binding Energy Distributions and the Hydration Free Energy of Protein Cytochrome C from All-Atom Simulations
journal, August 2012

  • Weber, Valéry; Asthagiri, D.
  • Journal of Chemical Theory and Computation, Vol. 8, Issue 9
  • DOI: 10.1021/ct300505b

Solvation Free Energy of the Peptide Group: Its Model Dependence and Implications for the Additive-Transfer Free-Energy Model of Protein Stability
journal, September 2013


Importance of Hydrophilic Hydration and Intramolecular Interactions in the Thermodynamics of Helix–Coil Transition and Helix–Helix Assembly in a Deca-Alanine Peptide
journal, December 2015

  • Tomar, Dheeraj S.; Weber, Valéry; Pettitt, B. Montgomery
  • The Journal of Physical Chemistry B, Vol. 120, Issue 1
  • DOI: 10.1021/acs.jpcb.5b09881

Proteins as Random Coils. I. Intrinsic Viscosities and Sedimentation Coefficients in Concentrated Guanidine Hydrochloride
journal, February 1967

  • Tanford, Charles.; Kawahara, Kazuo.; Lapanje, Savo.
  • Journal of the American Chemical Society, Vol. 89, Issue 4
  • DOI: 10.1021/ja00980a001

Adaptive biasing force method for scalar and vector free energy calculations
journal, April 2008

  • Darve, Eric; Rodríguez-Gómez, David; Pohorille, Andrew
  • The Journal of Chemical Physics, Vol. 128, Issue 14
  • DOI: 10.1063/1.2829861

VMD: Visual molecular dynamics
journal, February 1996