Bulletin of the American Physical Society
APS March Meeting 2018
Volume 63, Number 1
Monday–Friday, March 5–9, 2018; Los Angeles, California
Session H50: Physics of Proteins II: Experimental and Computational Studies on the Structure and Conformational Dynamics of ProteinsFocus
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Sponsoring Units: DBIO Chair: Aihua Xie, Oklahoma State University Room: LACC 511B |
Tuesday, March 6, 2018 2:30PM - 3:06PM |
H50.00001: Measuring Protein Intramolecular Dynamics with Terahertz Light: Functional Changes and Relevance to Biology Invited Speaker: Andrea Markelz As Austin and coworkers showed over 45 years ago [1], thermally activated motions are critical to protein function, however the characterization of these motions has been challenging. In the last 20 years new optical instrumentation in the critical terahertz (THz) frequency range has enabled unprecedented characterization of these dynamics revealing changes in the collectivity and orientation of motions with functional state for enzymes and photoactive proteins [2-5]. In this talk I will review measurements of protein intramolecular vibrations, their directionality and their impact on steering function. The various shortcomings of standard simulation methods to analyze the optical results will be discussed as well as possible strategies to overcome these. This work was supported by National Science Foundation MRI^2 grant DBI2959989, IDBR grant DBI1556359, and MCB grant MCB1616529, and the Department of Energy BES grant DE-SC0016317. |
Tuesday, March 6, 2018 3:06PM - 3:18PM |
H50.00002: Temperature Dependence of Confined Protein Hydration and Dynamics Djamila Lou, Ali Charkhesht, Vinh Nguyen The function and stability of proteins in water strongly depend on the temperature and conditions of the environment. The temperature dependence is thought to explain the denaturation of proteins at low and high temperatures, and the specific globular structure for protein function is determined by the hydrophobic effect. However, the strength of the hydrophobicity is strongly temperature dependent. Here, we have employed a very sensitive dielectric megahertz-to-terahertz frequency-domain spectroscopy system to probe lysozyme hydration shells and collective vibrational modes of lysozyme in water. Using the system, we explore the dielectric response of solvated lysozyme protein over a range of 50 MHz to 2 THz in a wide range of temperatures. The dielectric relaxation spectra reveal several polarization mechanisms at the molecular level with different time constants and dielectric strengths, reflecting the complexity of protein-water interactions. High-precision measurements of the hydration water and protein dynamics as a function of temperature provide the dynamical influence of protein on the temperature. Our results reveal critical information of protein dynamics and protein-water interfaces with temperature, which determine the biochemical functions and reactivity of proteins. |
Tuesday, March 6, 2018 3:18PM - 3:30PM |
H50.00003: Time Resolved Ice Formation in Protein Crystals Hakan Atakisi, David Moreau, Robert Thorne A combination of solvent nanoconfinement, fast cooling, and fast data collection enables ice-free protein crystallography between 180 and 260 K, even in crystals having large solvent cavities and large bulk-like solvent fractions. The time evolution of diffraction properties was measured for fast-cooled crystals of apoferritin (63% solvent content, 33.9 Å solvent cavities) and of thaumatin (58% solvent content, 12.4 Å solvent cavities) soaked in solutions containing between 0% and 40% w/v glycerol. While ice formation in external solvent occurs rapidly below 260 K, internal solvent is suppressed and occurs stochastically. Removing external solvent reliably produces ice-free diffraction at between 180 K and 260 K for at least seconds, sufficient for collection of complete data sets. At 200 to 240 K, crystal mosaicities are much smaller than those obtained at 100 K with lowest mosaicities from cryoprotectant-free crystals. While the internal solvent remains liquid, solvent transport within the crystal and structural relaxations of the protein molecules and of the crystal lattice can occur. These results make variable temperature crystallography viable for protein crystals with large solvent contents, and with weakly bound ligands that may be displaced by cryorpotectants. |
Tuesday, March 6, 2018 3:30PM - 3:42PM |
H50.00004: Void Distributions and Vibrational Response in Protein Cores John Treado, Zhe Mei, Jennifer Gaines, Lynne Regan, Corey O'Hern Proteins derive much of their stability from densely packed, hydrophobic residues that are shielded from solvent in protein cores. Our previous studies have shown that the packing fraction in protein cores is the same as that for jammed packings of purely repulsive, residue-shaped particles, which suggests that the protein backbone does not significantly affect how core residues pack. Here, we investigate the distribution of void space in protein cores and packings of residue-shaped particles. We show that packings of residue-shaped particles and protein cores possess similar connected void and free volume distributions. We also calculate the density of vibrational modes for packings of residue-shaped particles, and find an abundance of low frequency vibrational modes, which suggests the presence of low-energy collective motions of residues in protein cores. These results suggest that jammed packings of residue-shaped particles can serve as a mechanical analog for residues in protein cores, which can give insight into the response of protein cores to mutations. |
Tuesday, March 6, 2018 3:42PM - 3:54PM |
H50.00005: Studies of Voids in Proteins Zhe Mei, John Treado, Corey O'Hern, Lynne Regan Previous studies have shown that the hard-sphere plus stereochemical constraint model with explicit hydrogens can accurately predict the side-chain dihedral angle combinations of residues in protein cores. However, the side chain dihedral angle prediction accuracy decreases as the solvent accessible surface area of residues increases, for example near cavities and voids. We performed an analysis of internal cavities in proteins from a database of high-resolution protein crystal structures. We measured void size statistics and void locations in each protein. We correlate the motion of residues in response to mutations to their proximity to large cavities. We show that residues adjacent to larger cavities undergo increased backbone and side chain motion in response to mutations. |
Tuesday, March 6, 2018 3:54PM - 4:06PM |
H50.00006: Thermodynamic and kinetic scenarios of cooperative allosteric ligand binding in calmodulin Prithviraj Nandigrami, Daniel Gavazzi, John Portman Conformational dynamics are essential to a protein’s ability to control regulatory functions through |
(Author Not Attending)
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H50.00007: A Theory for Allosteric Temperature-Sensitive Transcriptional Factors Zechen Zhang, Tal Einav, Vahe Galstyan, Rob Phillips The MWC model is known to robustly model the allosteric transition of proteins. Recently the allostery theory has been shown consistent with transcriptional induction process engineered in E. coli. We are intrigued by the idea of induction through ligand binding that controls protein activity and we want to extend the allostery framework to incorporate protein activity dependence on other parameters such as temperature and light intensity. In this talk, we propose an allostery theory for the repressor activity, treating temperature as an "effective ligand" that could induce an allosteric transition. Specifically, the repressor protein can be treated as a two-state system with different conformational energies and vibrational density of states distributions. We show a potential application of the theory to model the thermal biological switch. |
Tuesday, March 6, 2018 4:18PM - 4:30PM |
H50.00008: Investigating the Protein Secondary Structure at the Nanoscale using Infrared Nano-Spectroscopy Max Eisele, Adrian Cernescu Scattering-type scanning near-field optical microscopy (s-SNOM) has become a key technology to study the chemical composition of organic materials at the nanoscale. This AFM-based technology exploits the strong confinement of light at the end of a sharp, metallic AFM tip to generate a nanoscale optical hotspot at the sample surface. Importantly, the amplitude and phase of the light within the optical hotspot is strongly influenced by the dielectric properties (absorption, reflectivity) of the sample directly below the tip. Phase and amplitude-resolved detection of the back-scattered radiation as function of position can therefore be used to extract the local optical properties at the sample surface with <10 nanometer precision. Utilizing broadband laser sources like a mid-infrared supercontinuum laser for tip illumination enables hyperspectral spectroscopic measurements with nanoscale spatial resolution. Embedded structural phases in organic semiconductors, biominerals, or biomolecules can now directly be visualized and characterized on the nanometer length scale. In this presentation we will introduce the basic principle of near-field microscopy and hyperspectral nanospectroscopy and address their impact and key applications in the field of organic materials |
Tuesday, March 6, 2018 4:30PM - 4:42PM |
H50.00009: In Silico Analysis of Anthrax Antitoxin CMG2-Fc: Glycosylation, Linker Design, and Binding Ability Austen Bernardi, Roland Faller CMG2-Fc is a synthetic, chimeric glycoprotein that serves as an antitoxin for anthrax. It is a dimer, with one glycosylation site per monomer. A synthetic linker is used to join the CMG2 and Fc domains. Since the CMG2 and Fc domains bind separate cofactors (Anthrax's Protective Agent and immune receptor FcγRIIIA, respectively), the linker could play a significant roll in the binding ability of each domain. Additionally, the glycosylation sites are located in close proximity to the linker and can affect the association of the CMG2 and Fc domains. In this work, we investigate different linkers and glycosylation profiles for CMG2-Fc, and elucidate how these variables affect structure and function. We employ standard molecular dynamics to study the structure and dynamics of CMG2-Fc variants, and use the method of well-tempered metadynamics to study the binding of CMG2-Fc and its cofactors. |
Tuesday, March 6, 2018 4:42PM - 4:54PM |
H50.00010: The Impact of Hydrodynamic Interactions on Protein Folding Rates Depends on Temperature Margaret Cheung, Fabio Zegarra, Dirar Homouz, Yossi Eliaz, Andrei Gasic Hydrodynamic interactions (HI) arise by the exchange of momentum between solvent particles and the particles immersed in solvent effectively coupling the movement of the entire system. However, the extent of the impact of HI on protein folding kinetics is controversial. Using a minimalist coarse-grained computer model and the theoretical framework of the Energy Landscape Theory (ELT) for protein folding, we revealed the effects of HI on the folding rates of two proteins with distinctive topologies: a 64-residue α/β chymotrypsin inhibitor 2 (CI2) protein, and a 57-residue β-barrel α-spectrin src-Homology 3 domain (SH3) protein. We find that the effect of HI on protein folding is temperature dependent. At a temperature greater than the folding temperature, HI drags the polymeric chain away from collapsing, resulting in a retarded folding rate. Conversely, at a temperature lower than the folding temperature, HI facilitates folding rates depending on the topology of a protein. Our investigation provides a general explanation of the impact of HI on protein folding. |
Tuesday, March 6, 2018 4:54PM - 5:06PM |
H50.00011: Gating of Membrane Protein Polyhedral Nanoparticles Mingyuan Ma, Di Li, Osman Kahraman, Christoph Haselwandter Membrane proteins and lipids can self-assemble into membrane protein polyhedral nanoparticles (MPPNs)—closed lipid bilayer vesicles with a polyhedral arrangement of membrane proteins. The closed surfaces of MPPNs, together with their well-defined symmetry and characteristic size, may permit structural studies of membrane proteins in the presence of transmembrane gradients. In particular, transmembrane gradients can be used to stabilize distinct conformational states of membrane proteins in MPPNs, such as the closed and open states of ion channels. We describe here a computational model of MPPN symmetry inspired by previous work on viral capsid self-assembly. Our model allows us to systematically explore the preferred symmetry of MPPNs as a function of the number of open and closed ion channels in MPPNs, and the difference in size of open and closed ion channels. Our results suggest practical strategies for the utilization of MPPNs as a novel method for the structural analysis of membrane proteins in controlled conformational states. |
Tuesday, March 6, 2018 5:06PM - 5:18PM |
H50.00012: Quantification of Subcellular Nanoparticle Size Distributions with Light Transmission Spectroscopy Alison Deatsch, Nan Sun, Carol Tanner, Steven Ruggiero We present measurements of the particle size distribution (PSD) of subcellular particles using Light Transmission Spectroscopy. In this work PSDs are established in two ways: (1) using our traditional approach of applying Mie theory to obtain PSDs from measured optical extinction spectra over a wavelength range of ~ 250 nm to 1000 nm and (2) with a new approach where the concentration of proteins is obtained directly from the magnitude of absorption peaks in the optical extinction spectra. In these ways we have successfully obtained PSDs for plant and animal cells over a wide size range: from ~ 2 nm to 3000 nm. These results reveal a power law dependence of particle concentration, N(D), with diameter, D, where N(D) ∝ D -α. We discuss values obtained for the power-law exponents, α, for cells (in the vicinity of 3) compared to other nanoparticle systems, and present primitive packing models. |
Tuesday, March 6, 2018 5:18PM - 5:30PM |
H50.00013: Investigating van der Waals Collective Behavior in Proteins via Interaction with Polarizable Ligands Travis Craddock, Jacob Hardy, Rajeev Jaundoo, Philip Kurian The assembly of complex macromolecular biological systems is often driven by weak non-covalent vdW dispersion interactions arising from electrodynamic correlations between instantaneous charge fluctuations in matter. Variations in these power laws can have a profound impact on observed properties. Here, we computationally investigate the effect of chemically unreactive ligands that act on proteins mainly via vdW dispersion forces. Specifically, we use inhalational anesthetics. While the exact mechanisms of anesthetic action are unknown, there is a known link between anesthetic potency and solubility in a non-polar medium. Anesthetic action is also related to an anesthetic’s hydrophobicity, permanent dipole, and polarizability, and is accepted to occur in non-polar regions within brain proteins. We use quantum chemistry calculations, and theoretical modeling of collective dipole interactions in proteins to investigate the effect of anesthetic gases on protein dynamics. In general these gases alter collective terahertz dipole oscillations. Our results emphasize the importance of collective electronic vibrational motions in proteins, how such motions contribute to overall protein interaction, and how interaction with polarizable ligands may alter such motions and interactions. |
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