Title

HELICAL STABILIZATION ON YAP1 PROTEIN FRAGMENTS

Introduction

Using molecular dynamics (MD) simulations, the preferred structure of a selected fragment of a specific protein in different environments may be determined. Multiple simulations were performed on three separate fragments of the Yap1 protein. The results provided classification of hydrophobic or hydrophilic helices determined from the structures resulting from vacuum and water simulations. It was also determined whether or not an ion would provide stabilization to a helix in the different environments. In addition, Steered Molecular Dynamics (SMD) simulations were performed to study the ion-helix interaction. Simulations were performed with the NAMD simulation program. To test a fragment’s hydrophobicity or hydrophilicity, a fragment was simulated in two different environments: vacuum and explicit water. Next, the stabilization effect of an ion on the helix was determined. An ion was placed near the protein fragment, once again, in both vacuum and water environments. Finally, NAMD was used to perform pulling (SMD) simulations. Two types of pulling SMD simulations may be used, constant force and constant velocity. In constant force simulations, the force applied to the SMD atom (the atom which the simulation parameters are being applied) remains constant (meaning the velocity must change to keep the force constant). In constant velocity simulations, the velocity of the atom is constant (meaning the reverse must take place, i.e., the force must change to keep the velocity constant). Once again, the pulling simulations were performed in both water and vacuum environments. The results and data were then generated, viewed, and/or analyzed with the VMD program. The results of the simulations of the fragment alone were determined by whether or not the fragment was hydrophilic or hydrophobic. If the peptide is hydrophilic, it would form an alpha-helix when (MD) simulated in water. Conversely, if the peptide is hydrophobic, it would form an alpha-helix when (MD) simulated in vacuum. Simulations where an ion was placed near the fragment provided some evidence of ionic stabilization on the helix, however the results were not concrete. In pulling simulations, three different results might be expected: the fragments could undergo a uniform unwinding, similar to pulling on a spring; the fragment could unwind randomly, with no recognizable pattern; the fragment could unwind at the anchored end, while the end near the ion maintains its helix structure, due to the ionic stabilization on the helix. In our pulling simulations, the pull on the ion caused a pull on the helix due to interactions, although the results were not entirely what was expected, especially in simulations that were ran in water environments. Future goals would include determining the work need be applied in order to break particular hydrogen bonds of the alpha helix structure. Analysis will allow the hydrogen bonds to be pinpointed, not only where, but when they are breaking. Combining this information with force-scripting techniques will allow calculation of the amount of work being applied at the corresponding times, yielding the amount of work needed to break a particular alpha helix hydrogen bond.

Location

DeRosa University Center, Stockton campus, University of the Pacific

Format

Poster Presentation

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Mar 25th, 10:00 AM Mar 25th, 3:00 PM

HELICAL STABILIZATION ON YAP1 PROTEIN FRAGMENTS

DeRosa University Center, Stockton campus, University of the Pacific

Using molecular dynamics (MD) simulations, the preferred structure of a selected fragment of a specific protein in different environments may be determined. Multiple simulations were performed on three separate fragments of the Yap1 protein. The results provided classification of hydrophobic or hydrophilic helices determined from the structures resulting from vacuum and water simulations. It was also determined whether or not an ion would provide stabilization to a helix in the different environments. In addition, Steered Molecular Dynamics (SMD) simulations were performed to study the ion-helix interaction. Simulations were performed with the NAMD simulation program. To test a fragment’s hydrophobicity or hydrophilicity, a fragment was simulated in two different environments: vacuum and explicit water. Next, the stabilization effect of an ion on the helix was determined. An ion was placed near the protein fragment, once again, in both vacuum and water environments. Finally, NAMD was used to perform pulling (SMD) simulations. Two types of pulling SMD simulations may be used, constant force and constant velocity. In constant force simulations, the force applied to the SMD atom (the atom which the simulation parameters are being applied) remains constant (meaning the velocity must change to keep the force constant). In constant velocity simulations, the velocity of the atom is constant (meaning the reverse must take place, i.e., the force must change to keep the velocity constant). Once again, the pulling simulations were performed in both water and vacuum environments. The results and data were then generated, viewed, and/or analyzed with the VMD program. The results of the simulations of the fragment alone were determined by whether or not the fragment was hydrophilic or hydrophobic. If the peptide is hydrophilic, it would form an alpha-helix when (MD) simulated in water. Conversely, if the peptide is hydrophobic, it would form an alpha-helix when (MD) simulated in vacuum. Simulations where an ion was placed near the fragment provided some evidence of ionic stabilization on the helix, however the results were not concrete. In pulling simulations, three different results might be expected: the fragments could undergo a uniform unwinding, similar to pulling on a spring; the fragment could unwind randomly, with no recognizable pattern; the fragment could unwind at the anchored end, while the end near the ion maintains its helix structure, due to the ionic stabilization on the helix. In our pulling simulations, the pull on the ion caused a pull on the helix due to interactions, although the results were not entirely what was expected, especially in simulations that were ran in water environments. Future goals would include determining the work need be applied in order to break particular hydrogen bonds of the alpha helix structure. Analysis will allow the hydrogen bonds to be pinpointed, not only where, but when they are breaking. Combining this information with force-scripting techniques will allow calculation of the amount of work being applied at the corresponding times, yielding the amount of work needed to break a particular alpha helix hydrogen bond.