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.
|Yonkunas, Michael; Buddhadev, Maiti; Flores Canales, Jose C et al. (2017) Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers. Biophys J 112:2291-2300|
|Earley, Lauriel F; Powers, John M; Adachi, Kei et al. (2017) Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11. J Virol 91:|
|Subramanian, Sandeep; Chaparala, Srilakshmi; Avali, Viji et al. (2016) A pilot study on the prevalence of DNA palindromes in breast cancer genomes. BMC Med Genomics 9:73|
|Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi (2016) Thermodynamic free energy methods to investigate shape transitions in bilayer membranes. Int J Adv Eng Sci Appl Math 8:88-100|
|Zhang, Yimeng; Li, Xiong; Samonds, Jason M et al. (2016) Relating functional connectivity in V1 neural circuits and 3D natural scenes using Boltzmann machines. Vision Res 120:121-31|
|Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4|
|Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58|
|Lee, Tai Sing (2015) The visual system's internal model of the world. Proc IEEE Inst Electr Electron Eng 103:1359-1378|
|Kuhlman, Chris J; Anil Kumar, V S; Marathe, Madhav V et al. (2015) Inhibiting diffusion of complex contagions in social networks: theoretical and experimental results. Data Min Knowl Discov 29:423-465|
|Jurkowitz, Marianne S; Patel, Aalapi; Wu, Lai-Chu et al. (2015) The YhhN protein of Legionella pneumophila is a Lysoplasmalogenase. Biochim Biophys Acta 1848:742-51|
Showing the most recent 10 out of 289 publications