Bulletin of the American Physical Society
Annual Meeting of the APS Four Corners Section
Volume 60, Number 11
Friday–Saturday, October 16–17, 2015; Tempe, Arizona
Session E9: Biological Physics IV: Polymer Dynamics |
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Chair: Michael Vershinin, University of Utah Room: MU228 |
Friday, October 16, 2015 3:17PM - 3:41PM |
E9.00001: Complexity and Dynamics of Disordered Proteins. Invited Speaker: Sara M. Vaiana Proteins are perhaps the simplest biological functioning units in living organisms. Their simple behavior emerges from the underlying complexity of the many interactions which hold them together. The cooperative nature of such interactions leads to a unique protein structure or ``fold'' which in turn allows function. Recently this notion has been challenged by the discovery of a new class of proteins, called Intrinsically Disordered Proteins (IDPs) which do not ``fold'' yet carry out important biological functions. Because IDPs sample many different conformations on very fast timescales their study requires the use of novel experimental techniques. When proteins fail to fold they can form highly stable, symmetric structures called amyloid fibers, leading to diseases such as Alzheimer's, Parkinson's and type II diabetes. I will discuss what we have learned so far on the physics of IDPs, using a novel nanosecond laser-pump spectrometer built in our lab. [Preview Abstract] |
Friday, October 16, 2015 3:41PM - 3:53PM |
E9.00002: The Role of Dynamics in the Disease Development of Human Ferritin Avishek Kumar, Tyler Glembo, Banu Ozkan After analyzing different protein families, we observed the alteration of dynamics through allostery leads to functional changes, suggesting that disease-associated mutations impair allosteric regulations, causing loss of function. In this study, we analyzed the dynamics of the wild-type light chain subunit of human ferritin protein along with the neutral and disease forms. We performed replica exchange molecular dynamics of wild-type and mutants to obtain dynamics; then, we computed the dynamic flexibility index (DFI) of each position for the wild-type and mutants. DFI quantifies the resilience of a position to a perturbation providing a flexibility/rigidity measurement for a given position. The DFI analysis reveals that neutral variants and the wild-type exhibit similar flexibility profiles in which critical positions act as hinges in controlling the overall motion. Disease mutations alter the conformational dynamics, making hinges more loose, thus impairing the allosterically regulated dynamics. [Preview Abstract] |
Friday, October 16, 2015 3:53PM - 4:05PM |
E9.00003: Rigidity Transition: From Random Networks To Jamming Varda Faghir Hagh, M.F. Thorpe We study the qualitative differences in the rigidity transition of three types of disordered networks: randomly diluted spring networks, stress-relieved networks obtained by diluting the stressed bonds and disk packing networks. Unlike randomly diluted networks the transition points of stress-relieved and jammed networks are globally isostatic. However they behave very differently when we add/remove one bond to/from their isostatic state. We introduce two new indices h and s that measure the average fractions of hinges and stressed bonds that appear as we remove or add one bond to the isostatic state of the networks. These indices characterize the high degree of self-organization at the jamming point where global changes occur by adding or removing only one bond. We then incorporate a new condition into stress-relieved networks, where at each site we insist that the Hilbert stability condition is obeyed. The Hilbert condition involves having at least three contacts at each site, with at least one contact in every semicircle. This introduces an isostatic state with a unique structure of Laman sub-graphs identical to the Laman sub-graphs of jamming that has similar h and s indices and exposes the underlying geometrical self-organization of jammed networks. [Preview Abstract] |
Friday, October 16, 2015 4:05PM - 4:17PM |
E9.00004: Protein dynamics elucidates the phenotypic effects of nsSNVs coupled to functionally critical residues Brandon Butler, Avishek Kumar, Sudhir Kumar, Banu Ozkan Biological processes are facilitated largely by protein-protein interactions. Thus, non-synonymous single nucleotide variants (nsSNVs) on interface sites can impair protein function. We investigated the conformational dynamics of interface sites on 333 complexes using a site-specific structural dynamic flexibility metric (DFI). We found interfaces have lower DFI as compared to non-interfaces. Moreover, interface sites with damaging nsSNVs were found to have significantly lower DFI than those with benign nsSNVs, which relates structural dynamics to functional significance. In a new analysis, we considered a small fraction of interface residues known as ``hotspots'', which account for a large portion of the total binding free energy. Hotspots are critical for function, but, importantly, residues that are dynamically coupled to them are also critical. Using a new dynamic measure, functional-DFI (fDFI), on the same set of complexes we considered hotspots as input for f-DFI and estimated their impact on other residues harboring nsSNVs. Based on the f-DFI results, dynamics-based metrics can be useful in assessing phenotypes of residues that are not obvious as critical for function but can be damaging since they are coupled to functionally critical residues. [Preview Abstract] |
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