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Constrained Unfolding of a Helical Peptide: Implicit versus Explicit Solvents.

Bureau HR, Merz DR, Hershkovits E, Quirk S, Hernandez R - PLoS ONE (2015)

Bottom Line: Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean force (PMF) along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents.The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents.Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational and Molecular Science and Technology, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States of America.

ABSTRACT
Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean force (PMF) along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents. Adaptive steered molecular dynamics (ASMD) has been seen to provide a significant computational advantage by limiting the spread of the trajectories in a staged approach. The contraction of the trajectories at the end of each stage can be performed by taking a structure whose nonequilibrium work is closest to the Jarzynski average (in naive ASMD) or by relaxing the trajectories under a no-work condition (in full-relaxation ASMD--namely, FR-ASMD). Both approaches have been used to determine the energetics and hydrogen-bonding structure along the pathway for unfolding of a benchmark peptide initially constrained as an α-helix in a water environment. The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents. Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

No MeSH data available.


Related in: MedlinePlus

Two-dimensional histogram of peptide-peptide and peptide-solvent hydrogen bonds for ALA10 structures in explicit, implicit, and vacuum along an ASMD pulling path.The color scale on the right from black to blue indicates the density of the points for that region of the map.
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pone.0127034.g008: Two-dimensional histogram of peptide-peptide and peptide-solvent hydrogen bonds for ALA10 structures in explicit, implicit, and vacuum along an ASMD pulling path.The color scale on the right from black to blue indicates the density of the points for that region of the map.

Mentions: The results presented here include the determination of the PMF using naive ASMD and FR-ASMD at varying pullng speeds in varying solvent conditions. Specifically, Fig 2 provides the direct comparison between the converged PMF for ALA10 in vacuum, implicit solvent, and explicit solvent. We used a pulling velocity of 1 Å/ns velocity for the vacuum and explicit solvent simulations, which is 10 times slower than our previous work, so as to confirm convergence with respect to the pulling velocity. [34] The convergence of the potentials are illustrated in Figs 3 and 4, for the explicit and implict solvents, respectively. The hydrogen-bond profiles along the ASMD pull are shown in Figs 5, 6 and 7, for ALA10 in vacuum, implicit solvent, and explicit solvent. A histogram of the intrapeptide hydrogen bonds as correlated with the actual or effective peptide-solvent hydrogen bonds in each of these three cases is shown in Fig 8. In the vacuum and implicit solvent cases, the peptide-solvent hydrogen bonds are effective in the sense that the relaxation of an all-atom water solvent around the fixed peptide is used to infer the hydrogen bonds to a solvent following the procedure described in Materials and Methods.


Constrained Unfolding of a Helical Peptide: Implicit versus Explicit Solvents.

Bureau HR, Merz DR, Hershkovits E, Quirk S, Hernandez R - PLoS ONE (2015)

Two-dimensional histogram of peptide-peptide and peptide-solvent hydrogen bonds for ALA10 structures in explicit, implicit, and vacuum along an ASMD pulling path.The color scale on the right from black to blue indicates the density of the points for that region of the map.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430545&req=5

pone.0127034.g008: Two-dimensional histogram of peptide-peptide and peptide-solvent hydrogen bonds for ALA10 structures in explicit, implicit, and vacuum along an ASMD pulling path.The color scale on the right from black to blue indicates the density of the points for that region of the map.
Mentions: The results presented here include the determination of the PMF using naive ASMD and FR-ASMD at varying pullng speeds in varying solvent conditions. Specifically, Fig 2 provides the direct comparison between the converged PMF for ALA10 in vacuum, implicit solvent, and explicit solvent. We used a pulling velocity of 1 Å/ns velocity for the vacuum and explicit solvent simulations, which is 10 times slower than our previous work, so as to confirm convergence with respect to the pulling velocity. [34] The convergence of the potentials are illustrated in Figs 3 and 4, for the explicit and implict solvents, respectively. The hydrogen-bond profiles along the ASMD pull are shown in Figs 5, 6 and 7, for ALA10 in vacuum, implicit solvent, and explicit solvent. A histogram of the intrapeptide hydrogen bonds as correlated with the actual or effective peptide-solvent hydrogen bonds in each of these three cases is shown in Fig 8. In the vacuum and implicit solvent cases, the peptide-solvent hydrogen bonds are effective in the sense that the relaxation of an all-atom water solvent around the fixed peptide is used to infer the hydrogen bonds to a solvent following the procedure described in Materials and Methods.

Bottom Line: Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean force (PMF) along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents.The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents.Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

View Article: PubMed Central - PubMed

Affiliation: Center for Computational and Molecular Science and Technology, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States of America.

ABSTRACT
Steered Molecular Dynamics (SMD) has been seen to provide the potential of mean force (PMF) along a peptide unfolding pathway effectively but at significant computational cost, particularly in all-atom solvents. Adaptive steered molecular dynamics (ASMD) has been seen to provide a significant computational advantage by limiting the spread of the trajectories in a staged approach. The contraction of the trajectories at the end of each stage can be performed by taking a structure whose nonequilibrium work is closest to the Jarzynski average (in naive ASMD) or by relaxing the trajectories under a no-work condition (in full-relaxation ASMD--namely, FR-ASMD). Both approaches have been used to determine the energetics and hydrogen-bonding structure along the pathway for unfolding of a benchmark peptide initially constrained as an α-helix in a water environment. The energetics are quite different to those in vacuum, but are found to be similar between implicit and explicit solvents. Surprisingly, the hydrogen-bonding pathways are also similar in the implicit and explicit solvents despite the fact that the solvent contact plays an important role in opening the helix.

No MeSH data available.


Related in: MedlinePlus