This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A quantitative measure and molecular-level interpretation of protein-lipid interactions is essential to understand the partitioning, folding and function of membrane-proteins, which make up a third of the human genome and the majority of all drug targets.
We aim to provide an understanding the physical rules that govern the assembly of membranes with their associated proteins using atomistic free energy molecular dynamics simulations. We will calculate free energy profiles of amino acid side chain analog molecules and ions to understand the energetics of permeation through a deformable lipid bilayer and to provide a renewed theoretical description of biological membranes. We will also continue to study the mechanisms of hydrophobic mismatch using polypeptides as model transmembrane segments and will begin simulations with polar sequences to understand new experimental data that challenges our hydrophobic matching concept. In addition, we will begin to explore the role of membrane composition on membrane deformability and permeability. We will also explore improved sampling methods for lipid bilayers. The results of this work have implications for a wide range of biological phenomena, including the activities of membrane proteins, antimicrobial and viral peptides, and bio-nanodevices.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR006009-20S1
Application #
8364254
Study Section
Special Emphasis Panel (ZRG1-BCMB-Q (40))
Project Start
2011-09-15
Project End
2013-07-31
Budget Start
2011-09-15
Budget End
2013-07-31
Support Year
20
Fiscal Year
2011
Total Cost
$1,094
Indirect Cost
Name
Carnegie-Mellon University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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