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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

An illustration of the three solvent regimes that are considered for the solvation of ALA10 in this work: vacuum (top), implicit solvent (center), and explicit TIP3P water solvent (bottom).In each frame, the ALA10 peptide is shown in a different configuration along the pulling coordinate.
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pone.0127034.g001: An illustration of the three solvent regimes that are considered for the solvation of ALA10 in this work: vacuum (top), implicit solvent (center), and explicit TIP3P water solvent (bottom).In each frame, the ALA10 peptide is shown in a different configuration along the pulling coordinate.

Mentions: Skinner and coworkers, [2, 3] for example, found that the environment plays a critical role in the structure formation of the putative helical segment in Rat and Human Amylin, but the question remains as to whether the solvent must be specified at all-atom resolution in order to obtain such effects in every case. The early work of Paci and Karplus, [4] assumed that an implicit solvent suffices in studying the structure and energetics for pulling titin. However, subsequent work on small alkanes [5] and ALA10 [6] suggests that the water model representing the solvent needs to be considered at least at a coarse-grained level so as to obtain the correct energetics and structure along the pathway. In our recent work, [7] we found that the energetics and the hydrogen-bonding pathway along the stretching of ALA10—whose structures are illustrated in Fig 1,—was quite different between vacuum and explicit solvents. However, Gumbart and coworkers [8] recently found a PMF for ALA10 in explicit water that differed from our previous result. As such, the determination of the correct pathway presents a significant test of the ASMD approach as well as the use of an implicit solvent model. Surprisingly, in the present work, we found that the overall pathway, in which internal hydrogen-bonds are broken and supplanted by contact to the solvent, is mostly recovered by the implicit solvent.


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

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

An illustration of the three solvent regimes that are considered for the solvation of ALA10 in this work: vacuum (top), implicit solvent (center), and explicit TIP3P water solvent (bottom).In each frame, the ALA10 peptide is shown in a different configuration along the pulling coordinate.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0127034.g001: An illustration of the three solvent regimes that are considered for the solvation of ALA10 in this work: vacuum (top), implicit solvent (center), and explicit TIP3P water solvent (bottom).In each frame, the ALA10 peptide is shown in a different configuration along the pulling coordinate.
Mentions: Skinner and coworkers, [2, 3] for example, found that the environment plays a critical role in the structure formation of the putative helical segment in Rat and Human Amylin, but the question remains as to whether the solvent must be specified at all-atom resolution in order to obtain such effects in every case. The early work of Paci and Karplus, [4] assumed that an implicit solvent suffices in studying the structure and energetics for pulling titin. However, subsequent work on small alkanes [5] and ALA10 [6] suggests that the water model representing the solvent needs to be considered at least at a coarse-grained level so as to obtain the correct energetics and structure along the pathway. In our recent work, [7] we found that the energetics and the hydrogen-bonding pathway along the stretching of ALA10—whose structures are illustrated in Fig 1,—was quite different between vacuum and explicit solvents. However, Gumbart and coworkers [8] recently found a PMF for ALA10 in explicit water that differed from our previous result. As such, the determination of the correct pathway presents a significant test of the ASMD approach as well as the use of an implicit solvent model. Surprisingly, in the present work, we found that the overall pathway, in which internal hydrogen-bonds are broken and supplanted by contact to the solvent, is mostly recovered by the implicit solvent.

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