Stability of Unfolded and Folded Protein Structures Using a 3D-RISM with the RMDFT

Yutaka Maruyama, Ayori Mitsutake

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Protein stability is determined by the characteristics of the protein itself as well as the surrounding solvent. Herein, we discuss the stability of the folded and unfolded structures of proteins obtained from Anton's long simulations (Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Shaw, D.E. Science, 2011, 334, 517-520). Specifically, the stabilities of CLN025, the WW domain variant GTT, the triple mutant of the redesigned protein G variant NuG2, and the de novo-designed three-helix bundle protein are investigated. The solvation free energy of the structures is calculated using the three-dimensional reference interaction site model with the reference-modified density functional theory. The total energy is given by the sum of the conformational energy and the solvation free energy, and their balance results in the stabilization of protein structure, as demonstrated by the correspondence between structures with the lowest total energy of all proteins to their native structures. Overall, these findings indicate that the total energy function is appropriate for evaluating the stability of protein folding systems. Moreover, decomposing the energy terms reveals that proteins achieve their stabilities from the balance between the conformational energy and the solvation free energy. In particular, the solvation entropy is the main contributor to the process of folding from more extended structures to compact structures. The native structure is more stable than the compact structure owing to competition between intramolecular and intermolecular interactions.

Original languageEnglish
Pages (from-to)9881-9885
Number of pages5
JournalJournal of Physical Chemistry B
Issue number42
Publication statusPublished - 2017 Oct 26

ASJC Scopus subject areas

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


Dive into the research topics of 'Stability of Unfolded and Folded Protein Structures Using a 3D-RISM with the RMDFT'. Together they form a unique fingerprint.

Cite this