Theoretical evidence for water insertion in .alpha.-helix bending: molecular dynamics of Gly30 and Ala30 in vacuo and in solution

DiCapua, Frank M.; Swaminathan, S.; Beveridge, David L.

doi:10.1021/ja00016a034

Cited by 52 publications

(74 citation statements)

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“…This implies that the valine side-chains are locked into their positions, from which they unravel only successively upon unfolding. It has been shown in MD simulations that helix denaturation follows from the solvent molecules replacing the regular ~-helical hydrogen bonds (DiCapua et al, 1991;Tirado-Rives & Jorgensen, 1991;De Loof et al, 1992). In the SP-C simulations the bulky hydrophobic side-chains of valine, leucine and isoleucine residues effectively keep the solvent molecules away from approaching the backbone amide groups and competing for the s-helical hydrogen bonds in polar media.…”

Section: Discussionmentioning

confidence: 99%

“…Several MD-simulations of s-helical polypeptides in aqueous solution have been reported (DiCapua et al, 1991;Soman et al, 1991;Tirado-Rives & Jorgensen, 1991;Daggett & Levitt, 1992;De Loof et al, 1992;van Buuren & Berendsen, 1993). Except for polyalanine helices (DiCapua et al, 1991;Daggett & Levitt, 1992) the s-helical starting conformation unfolds within a simulation period of a few hundred picoseconds at room temperature.…”

Section: Introductionmentioning

confidence: 99%

“…Except for polyalanine helices (DiCapua et al, 1991;Daggett & Levitt, 1992) the s-helical starting conformation unfolds within a simulation period of a few hundred picoseconds at room temperature. This is in line with experimental CD and NMR data concerning helicity of these isolated peptide fragments in solution, which indicate that the helical structure is in rapid equilibrium with other conformational states.…”

Section: Introductionmentioning

confidence: 99%

“…In previously published MD-simulations it has been shown that water molecules disrupt the helical structure by penetrating into the core of the peptide and replacing hydrogen bonds between the backbone carbonyls and amide protons (DiCapua et al, 1991;Tirado-Rives & Jorgensen, 1991;De Loof et al, 1992). The solvent molecule's size, polarity and hydrogen-bonding ability affect the interaction of solvent molecules with the protein backbone.…”

Section: Introductionmentioning

confidence: 99%

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Abstracts and Indexes

Atlas¹,

Snyder²

2014

Using the Biological Literature

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A series of three molecular dynamics simulations at 300 K in explicit solvent environments of chloroform, methanol and water has been performed on the pulmonary surfactant lipoprotein, SP-C, comprising several consecutive valine residues in order to investigate the stability of the u-helical conformation. Two additional simulations were performed on truncated SP-C with a five-residue N-terminal deletion at 300 K and 500 K in water, the high temperature run in order to increase the rate of peptide denaturation.Indications of destabilization appear in chloroform during 1 ns while the SP-C m-helix is remarkably stable during 1 ns in methanol and water. In particular the polyvalyl part comprising residues Va115 to Va121 remains intact even at elevated temperature, and the valines do not disrupt the u-helical conformation. The valyl-rotamer sampling is partly restricted. Unfolding takes place successively along the primary sequence starting from the C-terminal end. Factors affecting polypeptide stability in molecular dynamics simulations are addressed. The intrinsic helix-forming tendency of valine residues and its dependence on the sequence context, and the role of the solvent environment in stabilizing or destabilizing an u-helical fold, are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Abstracts and Indexes

Atlas¹,

Snyder²

2014

Using the Biological Literature

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“…The results presented in this article are presumably due to helix packing restraints that mimic the helical distortions caused by solvent. One of the future directions of this work involves investigations on the same system but including water molecules, in a study similar to the one carried out w x by DiCapua et al 36 .…”

Section: Helical Distortions At the Dimer Interfacementioning

confidence: 99%

Computational analysis of variants of the operator binding domain of the bacteriophage ? repressor

Kombo

Ravishanker

Rackovsky

et al. 1999

Int. J. Quant. Chem.

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ABSTRACT:In a continuing effort to understand the molecular basis of the dimerization-coupled DNA-binding activity of the bacteriophage repressor protein, we analyzed results from conformational energy computations on the wild-type repressor protein and its mutants. We find that the hydrogen bonds between the peptide carbonyl oxygen of Tyr-85 and the peptide NH group of the residue at position 89 in active mutants are longer and less linear than their corresponding ones in inactive mutants. This is due to the outward tilting of the carbonyl oxygen of Tyr-85 from the helix axis in active mutants, which, in many cases, results in disruption of its i to the i q 4 hydrogen bond involving this residue. The helical and hydrogen-bond parameters computed for both classes of mutants were compared with the results obtained by others in the analysis of X-ray-derived crystal structures of ␣-helices in globular proteins. We find that the packing of ␣-helices at the dimer interface of active and inactive mutants results in a hydrogen-bonding geometry for the carbonyl group of Tyr-85 that is similar to that found in ␣-helices with and without CO groups hydrogen-bonded to a solvent molecule,

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Curious structure in “canonical” alanine-based peptides

Shirley

Brooks

1997

Proteins

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We have performed all atom simulations of blocked peptides of the form (AAXAA)3, where X = Gln, Asn, Glu, Asp, Arg, and Lys with explicit water molecules to examine the interactions between side chains spaced i,i-5 in the sequence. Although side chains in this i,i-5 arrangement are commonly believed to be noninteracting, we have observed the formation of unusual i,i-5 main chain hydrogen bonding in such sequences with positively charged residues (Lys) as well as polar uncharged groups (Gln). Our results are consistent with the unusual percentage of hydrogen bonding curves produced by amide exchange measurements on the well-studied sequence acetyl-(AAQAA)3-amide in water (Shalongo, W., Dugad, L., Stellwagen, E. J. Am. Chem. Soc. 116:8288-8293, 1994). Analysis of our simulations indicated that the glutamine side chain showed the greatest propensity to support pi helix formation and that the i,i-5 intramolecular hydrogen bonds were stabilized by water-bridging side chain interactions. This intermittent formation of the unusual pi helix structure was observed for up to 23% of the total simulation time in some residues in (AAQAA)3. Control studies on peptides with glutamine side chains spaced i,i-3, i,i-4 and i,i-6 did not reveal similar unique structures, providing stronger evidence for the unique role side chain interactions with i,i-5 spacing.

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Theoretical evidence for water insertion in .alpha.-helix bending: molecular dynamics of Gly30 and Ala30 in vacuo and in solution

Cited by 52 publications

References 0 publications

Abstracts and Indexes

Abstracts and Indexes

Computational analysis of variants of the operator binding domain of the bacteriophage ? repressor

Curious structure in “canonical” alanine-based peptides

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