Solvation free energies of alanine peptides

The effect of flexibility

Hironori Kokubo, Robert C. Harris, Dilipkumar Asthagiri, Bernard Pettitt

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The electrostatic (ΔGel), van der Waals cavity-formation (ΔGvdw), and total (ΔG) solvation free energies for 10 alanine peptides ranging in length (n) from 1 to 10 monomers were calculated. The free energies were computed both with fixed, extended conformations of the peptides and again for some of the peptides without constraints. The solvation free energies, ΔGel, and components ΔGvdw, and ΔG, were found to be linear in n, with the slopes of the best-fit lines being γel, γvdw, and γ, respectively. Both γel and γ were negative for fixed and flexible peptides, and γvdw was negative for fixed peptides. That γvdw was negative was surprising, as experimental data on alkanes, theoretical models, and MD computations on small molecules and model systems generally suggest that γvdw should be positive. A negative γvdw seemingly contradicts the notion that ΔGvdw drives the initial collapse of the protein when it folds by favoring conformations with small surface areas. When we computed ΔGvdw for the flexible peptides, thereby allowing the peptides to assume natural ensembles of more compact conformations, γvdw was positive. Because most proteins do not assume extended conformations, a ΔGvdw that increases with increasing surface area may be typical for globular proteins. An alternative hypothesis is that the collapse is driven by intramolecular interactions. We find few intramolecular H-bonds but show that the intramolecular van der Waals interaction energy is more favorable for the flexible than for the extended peptides, seemingly favoring this hypothesis. The large fluctuations in the vdw energy may make attributing the collapse of the peptide to this intramolecular energy difficult.

Original languageEnglish
Pages (from-to)16428-16435
Number of pages8
JournalJournal of Physical Chemistry B
Volume117
Issue number51
DOIs
StatePublished - Dec 27 2013

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Solvation
alanine
Alanine
Peptides
Free energy
peptides
solvation
flexibility
free energy
Gels
gels
Conformations
cavities
proteins
Proteins
Alkanes
Paraffins
alkanes
energy
Electrostatics

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Solvation free energies of alanine peptides : The effect of flexibility. / Kokubo, Hironori; Harris, Robert C.; Asthagiri, Dilipkumar; Pettitt, Bernard.

In: Journal of Physical Chemistry B, Vol. 117, No. 51, 27.12.2013, p. 16428-16435.

Research output: Contribution to journalArticle

Kokubo, Hironori ; Harris, Robert C. ; Asthagiri, Dilipkumar ; Pettitt, Bernard. / Solvation free energies of alanine peptides : The effect of flexibility. In: Journal of Physical Chemistry B. 2013 ; Vol. 117, No. 51. pp. 16428-16435.
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