Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

Statistical Mechanical Model of Transport Receptor Binding in the Nuclear Pore Complex

The Nuclear Pore Complex (NPC) is a large protein complex that controls the flow of proteins and mRNA into and out of the nuclei of eukaryotic cells. A major component of the NPC consists of natively unfolded nucleoporin (nup) proteins, which are anchored on the inside of a cylindrical pore scaffold. They form a polymer brush that assists in the regulation of cargo flow from nucleus to cytoplasm. Large molecules that enter/leave the nucleus must attach themselves to special receptor proteins that ferry the cargo molecules in/out of nucleus. Via hydrophobic contacts between the receptor protein and the nup filaments, the receptor proteins bind weakly and reversibly to the nup filaments and make their way through the pore, via a mechanism that is at present unknown. The complexity of the in vivo NPC motivates construction of coarse-grained models that can capture some of its essential features while retaining computational tractability. We have developed such a model, focusing particularly on the interactions of this polymer brush with solution phase nanoparticles that are attractive to brush monomers (mimicking the attraction of receptor proteins to hydrophobic segments of nup filaments in the NPC). These attractions cause the nanoparticles to infiltrate into the polymer brush and alter its brush morphology. We have developed a Self-Consistent Field Theory model to analyze the equilibrium properties of the brush-nanoparticle system in an approximate but computationally efficient manner [1]. In addition, we have performed large scale coarse-grained Molecular/Langevin Dynamics simulations to explore the same properties [2, 3]. A variety of results pertaining to collapse/expansion of the brush upon nanoparticle infiltration will be presented. Their relevance to the in vivo mechanism of NPC operation will be stressed [4].


    1. Opferman, M.G., R.D. Coalson, D. Jasnow, and A. Zilman, The Morphology of Polymer Brushes Infiltrated by Attractive Nanoinclusions of Various Sizes. Langmuir, 2013. 9: p. 8584-8591.

    2. Nasrabad, A.E., D. Jasnow, A. Zilman, and R.D. Coalson, Precise Control of Polymer Coated Nanopores by Nanoparticle Additives: Insights from Computational Modeling. J. Chem. Phys., 2016. 145: p. 064901:1-5.

    3. Ozmaian, M., D. Jasnow, A.F. Nasrabad, A. Zilman, and R.D. Coalson, Effects of Cross-Linking on Partitioning of Nanoparticles into a Polymer Brush: Coarse-Grained Simulations Test Simple Approximate Theories. J. Chem. Phys., 2018. 148: p. 024902:1-12.

    4. Vovk, A., C. Gu, M.G. Opferman, L.E. Kapinos, L.R. YH., R.D. Coalson, D. Jasnow, and A. Zilman, Simple Biophysics Underpins Collective Conformations of the Intrinsically Disordered Proteins of the Nuclear Pore Complex. eLife, 2016. 5: p. 10785:1-29.

Rob D. Coalson

Dept. of Chemistry
University of Pittsburgh
Pittsburgh PA US

Email: coalson@pitt.edu