From dongxu@sciences.sdsu.edu Fri May 4 04:22:13 2007
From: dongxu@sciences.sdsu.edu (Dong Xu)
Date: Thu, 3 May 2007 20:22:13 -0700
Subject: [compsci] Reminder: CSRC Colloquium on Friday -- H-RAS PROTEIN IN A DMPC BILAYER: COMPUTATIONAL ANALYSIS OF INSERTION FREE ENERGY AND MEMBRANE STRUCTURE PERTURBATION
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Title: H-RAS PROTEIN IN A DMPC BILAYER: COMPUTATIONAL ANALYSIS OF
INSERTION FREE ENERGY AND MEMBRANE STRUCTURE PERTURBATION
Date: May 4, 2007
Time: 4:00 PM
Location: GMCS 214
Speaker:
Alemayehu Gorfe
Department of Chemistry and Biochemistry
University of California at San Diego
Abstract:
Ras proteins are GTPases that mediate signal transduction pathways
that control cell growth and proliferation. They are active when
anchored to the inner surface of plasma membrane by inserting their
lipid modified side chains into the hydrophobic core of the membrane.
The structure of the protein-membrane complex was not known. Using
modeling and molecular dynamics simulations, we have recently
characterized the structure of the full-length H-ras protein in a DMPC
bilayer [Gorfe AA, Hanzel-Bayer M, Abankwa D, Hancock JF and McCammon
JA, J. Med. Chem., 2007]. We found that ras binding to membrane
involves, in addition the anchor, a direct interaction with the
membrane phosphates of positively charged residues from either the
linker or the catalytic domain. These two modes of interaction
differently affect both the orientation of the catalytic domain
relative to the membrane plane and the structure and dynamics of the
bilayer. Moreover, we observed differential localization of the
backbone of the anchor when it is inserted alone versus together with
the linker or the linker and the GDP/GTP bound catalytic domain. We
have now computed the potential-of-mean-force for the insertion of the
lipid-anchor into a DMPC bilayer. This data enabled us derive a
possible mechanism for the membrane microdomain preferences of H-ras
and its fragments. I will discuss these recent computational results
and highlight their biological significance using experimental data
generated by our collaborators.
Host: Sam Kassegne
For future events, please visit our web site at:
http://www.csrc.sdsu.edu/csrc/events/colloquium/
*******************************************
Dong Xu
PhD Student
Computational Science Program
San Diego State University
Phone: 619-594-2710
Email: dongxu@sciences.sdsu.edu
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Content-Disposition: inline
Title: H-RAS PROTEIN IN A DMPC BILAYER: COMPUTATIONAL ANALYSIS OF
INSERTION FREE ENERGY AND MEMBRANE STRUCTURE PERTURBATION
Date: May 4, 2007
Time: 4:00 PM
Location: GMCS 214
Speaker:
Alemayehu Gorfe
Department of Chemistry and Biochemistry
University of California at San Diego
Abstract:
Ras proteins are GTPases that mediate signal transduction pathways
that control cell growth and proliferation. They are active when
anchored to the inner surface of plasma membrane by inserting their
lipid modified side chains into the hydrophobic core of the membrane.
The structure of the protein-membrane complex was not known. Using
modeling and molecular dynamics simulations, we have recently
characterized the structure of the full-length H-ras protein in a DMPC
bilayer [Gorfe AA, Hanzel-Bayer M, Abankwa D, Hancock JF and McCammon
JA, J. Med. Chem., 2007]. We found that ras binding to membrane
involves, in addition the anchor, a direct interaction with the
membrane phosphates of positively charged residues from either the
linker or the catalytic domain. These two modes of interaction
differently affect both the orientation of the catalytic domain
relative to the membrane plane and the structure and dynamics of the
bilayer. Moreover, we observed differential localization of the
backbone of the anchor when it is inserted alone versus together with
the linker or the linker and the GDP/GTP bound catalytic domain. We
have now computed the potential-of-mean-force for the insertion of the
lipid-anchor into a DMPC bilayer. This data enabled us derive a
possible mechanism for the membrane microdomain preferences of H-ras
and its fragments. I will discuss these recent computational results
and highlight their biological significance using experimental data
generated by our collaborators.
Host: Sam Kassegne
For future events, please visit our web site at:
http://www.csrc.sdsu.edu/csrc/events/colloquium/
*******************************************
Dong Xu
PhD Student
Computational Science Program
San Diego State University
Phone: 619-594-2710
Email:
dongxu@sciences.sdsu.edu
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