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ASU Scholarship Showcase


This growing collection consists of scholarly works authored by ASU-affiliated faculty, students and community members, and contains many open access articles. ASU-affiliated authors are encouraged to Share Your Work in the ASU Digital Repository.


Date Range
2006 2017


In proteins, functional divergence involves mutations that modify structure and dynamics. Here we provide experimental evidence for an evolutionary mechanism driven solely by long-range dynamic motions without significant backbone adjustments, catalytic group rearrangements, or changes in subunit assembly. Crystallographic structures were determined for several reconstructed ancestral proteins belonging to a GFP class frequently employed in superresolution microscopy. Their chain flexibility was analyzed using molecular dynamics and perturbation response scanning. The green-to-red photoconvertible phenotype appears to have arisen from a common green ancestor by migration of a knob-like anchoring region away from the active site diagonally across the β barrel fold. …

Contributors
Kim, Hanseong, Zou, Taisong, Modi, Chintan, et al.
Created Date
2015-01-06

Protein evolution is most commonly studied by analyzing related protein sequences and generating ancestral sequences through Bayesian and Maximum Likelihood methods, and/or by resurrecting ancestral proteins in the lab and performing ligand binding studies to determine function. Structural and dynamic evolution have largely been left out of molecular evolution studies. Here we incorporate both structure and dynamics to elucidate the molecular principles behind the divergence in the evolutionary path of the steroid receptor proteins. We determine the likely structure of three evolutionarily diverged ancestral steroid receptor proteins using the Zipping and Assembly Method with FRODA (ZAMF). Our predictions are within …

Contributors
Glembo, Tyler, Farrell, Daniel W., Gerek, Z. Nevin, et al.
Created Date
2012-03-29

Measurements on embryonic epithelial tissues in a diverse range of organisms have shown that the statistics of cell neighbor numbers are universal in tissues where cell proliferation is the primary cell activity. Highly simplified non-spatial models of proliferation are claimed to accurately reproduce these statistics. Using a systematic critical analysis, we show that non-spatial models are not capable of robustly describing the universal statistics observed in proliferating epithelia, indicating strong spatial correlations between cells. Furthermore we show that spatial simulations using the Subcellular Element Model are able to robustly reproduce the universal histogram. In addition these simulations are able to …

Contributors
Sandersius, Sebastian, Chuai, Manil, Weijer, Cornelis J., et al.
Created Date
2011-04-29

Mechanical interactions between cells and their microenvironment dictate cell phenotype and behavior, calling for cell mechanics measurements in three-dimensional (3D) extracellular matrices (ECM). Here we describe a novel technique for quantitative mechanical characterization of soft, heterogeneous samples in 3D. The technique is based on the integration of atomic force microscopy (AFM) based deep indentation, confocal fluorescence microscopy, finite element (FE) simulations and analytical modeling. With this method, the force response of a cell embedded in 3D ECM can be decoupled from that of its surroundings, enabling quantitative determination of the elastic properties of both the cell and the matrix. We …

Contributors
Staunton, Jack, Doss, Bryant, Lindsay, Stuart, et al.
Created Date
2016-01-27

Transmembrane proteins are responsible for transporting ions and small molecules across the hydrophobic region of the cell membrane. We are reviewing the evidence for regulation of these transport processes by interactions with the lipids of the membrane. We focus on ion channels, including potassium channels, mechanosensitive and pentameric ligand gated ion channels, and active transporters, including pumps, sodium or proton driven secondary transporters and ABC transporters. For ion channels it has been convincingly shown that specific lipid-protein interactions can directly affect their function. In some cases, a combined approach of molecular and structural biology together with computer simulations has revealed …

Contributors
Denning, Elizabeth J., Beckstein, Oliver, College of Liberal Arts and Sciences, et al.
Created Date
2013-08-12

Escherichia coli NhaA is a prototype sodium-proton antiporter, which has been extensively characterized by X-ray crystallography, biochemical and biophysical experiments. However, the identities of proton carriers and details of pH-regulated mechanism remain controversial. Here we report constant pH molecular dynamics data, which reveal that NhaA activation involves a net charge switch of a pH sensor at the entrance of the cytoplasmic funnel and opening of a hydrophobic gate at the end of the funnel. The latter is triggered by charging of Asp164, the first proton carrier. The second proton carrier Lys300 forms a salt bridge with Asp163 in the inactive …

Contributors
Huang, Yandong, Chen, Wei, Dotson, David, et al.
Created Date
2016-10-06

Diverse classes of proteins function through large-scale conformational changes and various sophisticated computational algorithms have been proposed to enhance sampling of these macromolecular transition paths. Because such paths are curves in a high-dimensional space, it has been difficult to quantitatively compare multiple paths, a necessary prerequisite to, for instance, assess the quality of different algorithms. We introduce a method named Path Similarity Analysis (PSA) that enables us to quantify the similarity between two arbitrary paths and extract the atomic-scale determinants responsible for their differences. PSA utilizes the full information available in 3N-dimensional configuration space trajectories by employing the Hausdorff or …

Contributors
Seyler, Sean, Kumar, Avishek, Thorpe, Michael, et al.
Created Date
2015-10-21

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme’s ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the …

Contributors
Larrimore, Katherine, Kazan, I. Can, Kannan, Latha, et al.
Created Date
2017-09-05

Electron transfer between redox proteins participating in energy chains of biology is required to proceed with high energetic efficiency, minimizing losses of redox energy to heat. Within the standard models of electron transfer, this requirement, combined with the need for unidirectional (preferably activationless) transitions, is translated into the need to minimize the reorganization energy of electron transfer. This design program is, however, unrealistic for proteins whose active sites are typically positioned close to the polar and flexible protein-water interface to allow inter-protein electron tunneling. The high flexibility of the interfacial region makes both the hydration water and the surface protein …

Contributors
Matyushov, Dmitry, College of Liberal Arts and Sciences, Department of Physics, et al.
Created Date
2013

First column reports protein name as reported in O′Brien et al. [24]; second column reports where is the folding speed (in the units of ) for the slowest folding domain; third column reports abundance value (in ppm) from PaxDB Integrated list [23]. doi:10.1371/journal.pone.0112701.s001 First column reports Open Reading Frame as reported in YRC [22]; second column reports where is the folding speed for the slowest folding domain in the units of ; third column reports abundance value (in ppm) from PaxDB Integrated list [23]. doi:10.1371/journal.pone.0112701.s002 First column reports Open Reading Frame as reported in YRC [22]; second column reports halflife …

Contributors
Zou, Taisong, Williams, Nickolas, Ozkan, Sefika, et al.
Created Date
2014-11-13