DOI: 10.1002/prot.340100306. Proline in α‐helix: Stability and conformation studied by dynamics simulation

Proline in α‐helix: Stability and conformation studied by dynamics simulation

10.1002/prot.340100306

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractFree‐energy simulations have been used to estimate the change in the conformational stability of short polyalanine α‐helices when one of the alanines is replaced by a proline residue. For substituting proline in the middle of the helix the change in free energy of folding (ΔΔG°) was calculated as 14 kJ/mol (3.4 kcal/mol), in excellent agreement with the one available experimental value. The helix containing proline was found to be strongly kinked; the free energy for reducing the angle of the kink from 40° to 15° was calculated, and found to be small. A tendency to alternate hydrogen bonding schemes was observed in the proline‐containing helix. These observations for the oligopeptide agree well with the observation of a range of kink angles (18–35°) and variety of hydrogen bonding schemes, in the rare instances where proline occurs in helices in globular proteins. For substituting proline at the N‐terminus of the helix the change in free energy of folding (ΔΔG°) was calculated as −4 kJ/mol in the first helical position (N1) and +6 kJ/mol in the second helical position (N2). The observed frequent occurrence of proline in position N1 in α‐helices in proteins therefore has its origin in stability differences of secondary structure. The conclusion reached here that proline may be a better helix former in position N1 than (even) alanine, and thus be a helix initiator may be testable experimentally by measurements of fraction helical conformation of individual residues in oligopeptides of appropriate sequence. The relevance of these results in regards to the frequent occurrence of proline‐containing helices in certain membrane proteins is discussed.

Bibliography

Yun, R. H., Anderson, A., & Hermans, J. (1991). Proline in Î±âhelix: Stability and conformation studied by dynamics simulation. Proteins: Structure, Function, and Bioinformatics, 10(3), 219â228. Portico.

Authors 3

R. H. Yun (first)
Amil Anderson (additional)
Jan Hermans (additional)

References 35 Referenced 117

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{'key': 'e_1_2_1_11_2', 'first-page': '43', 'volume-title': 'Molecular Dynamics and Protein Structure', 'author': 'Berendsen H. J. C.', 'year': '1985'} / Molecular Dynamics and Protein Structure by Berendsen H. J. C. (1985)
10.1016/0097-8485(84)85020-2
10.1111/j.1749-6632.1986.tb20933.x
{'key': 'e_1_2_1_13_3', 'first-page': '1', 'volume-title': 'Computer Simulation of Biomolecular Systems', 'author': 'Beveridge D. L.', 'year': '1989'} / Computer Simulation of Biomolecular Systems by Beveridge D. L. (1989)
van Gunsteren W. F.Methods for calculation of free energies and binding constants: Successes and problems.Computer Simulation of Biomolecular Systems.:27–59.
10.1021/ja00204a027
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As mentioned bondlengths are kept fixed with Shake. The use of λ3and λ5as multipliers is equivalent to varying both ϵ and σ3as λ when using the common ϵ–σ form of the Lennard–Jones equation.
Hermans J. Yun R. H. Anderson A. G.Precision of free energies calculated by molecular dynamics simulations of peptides in solution.J. Phys. Chem. submitted for publication.
As in earlier work we refer to the neighborhoods of the four free‐energy minima of the alanine dipeptide as the β‐ αR αL andCconformations using already familiar terms less stringently. (Roughly speaking each conformation corresponds to a different quadrant of the Ramachandran diagram e.g. for the β‐conformation −180° < ϕ < 0 0 < Ψ < 180° for the αRconformation −180° < ϕ < 0 −180° < Ψ < 0°.)
10.1021/ja01091a003
10.1126/science.2837824
10.1016/0022-2836(68)90237-4
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Computed as the difference for the alanine and proline dipeptides of free energies given by ‐kTln ∫∫ exp[–ΔG°/kT]dϕdΨ where Δq° represents conformational free energy.
10.1016/0022-2836(85)90049-X
10.1016/S0022-2836(77)80111-3
10.1016/0022-2836(88)90319-1
A very strongly kinked proline‐containing helix is found in melittin; in this helix an adjacent glycine residue having a nonhelical conformation serves as a “hinge” which interrupts the hydrogen bonding pattern but without intervention of a water molecule.28
10.1016/S0021-9258(20)65097-9
10.1002/bip.360260910
10.1073/pnas.84.15.5087
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{'key': 'e_1_2_1_33_2', 'first-page': '14192', 'article-title': 'Structure‐function studies of bacteriorhodopsin VIII. Substitutions of the membrane‐embedded prolines 50, 91, 186: The effects are determined by the substituting amino acids', 'volume': '264', 'author': 'Mogi T.', 'year': '1989', 'journal-title': 'J. Biol. Chem.'} / J. Biol. Chem. / Structure‐function studies of bacteriorhodopsin VIII. Substitutions of the membrane‐embedded prolines 50, 91, 186: The effects are determined by the substituting amino acids by Mogi T. (1989)
10.1016/S0022-2836(05)80271-2

Dates

Type	When
Created	20 years, 3 months ago (May 28, 2005, 9:10 p.m.)
Deposited	1 year, 10 months ago (Oct. 22, 2023, 9:33 p.m.)
Indexed	1 week ago (Aug. 29, 2025, 6:48 a.m.)
Issued	34 years, 6 months ago (March 1, 1991)
Published	34 years, 6 months ago (March 1, 1991)
Published Online	21 years, 7 months ago (Feb. 3, 2004)
Published Print	34 years, 6 months ago (March 1, 1991)

Funders 0

None

BibTeX

@article{Yun_1991, title={Proline in α‐helix: Stability and conformation studied by dynamics simulation}, volume={10}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.340100306}, DOI={10.1002/prot.340100306}, number={3}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Yun, R. H. and Anderson, Amil and Hermans, Jan}, year={1991}, month=mar, pages={219–228} }

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