Bulletin of the American Physical Society
APS March Meeting 2021
Volume 66, Number 1
Monday–Friday, March 15–19, 2021; Virtual; Time Zone: Central Daylight Time, USA
Session E12: Physics of Proteins IIFocus Live
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Sponsoring Units: DBIO DPOLY Chair: Wouter Hoff, Oklahoma State Univ - Stillwater; Dongping Zhong, Ohio State Univ - Columbus |
Tuesday, March 16, 2021 8:00AM - 8:12AM Live |
E12.00001: Towards integrative structural biology of proteins at ultra-high resolution Wouter Hoff, Junpei Matsuo, Takashi Kikukawa, Tomotsumi Fujisawa, Masashi Unno, Aihua Xie Integrative structural biology is an emerging approach in which results obtained through different experimental methods are integrated using a common computational framework. Thus far, integrative structural biology has focused mainly on resolving large macromolecular complexes and their dynamics. Here we propose to use integrative structural biology to obtain insights at very high structural resolution. We use information from X-ray crystallography and combine it with results from different vibrational spectroscopic approaches, particularly FTIR spectroscopy, Raman spectroscopy, and Raman Optical Activity (ROA) spectroscopy, to better understand photoreceptor proteins. In ROA spectroscopy the detection of differences in Raman scattering when using left polarized light and right polarized light is increasingly allowing insights into functionally important structural distortions of the light-absorbing chromophore at the active site of photoreceptors. These results are then integrated using quantum chemical calculations. We illustrate this approach for two different types of photoreceptors: photoactive yellow protein and microbial rhodopsins. |
Tuesday, March 16, 2021 8:12AM - 8:24AM Live |
E12.00002: Probing Dynamics of Hemeproteins in Solution by the High Sensitivity Dielectric Terahertz Spectroscopy Luan Doan, Sarah Seay, Vinh Q Nguyen Hemeproteins constitute a large class of biomolecules and play a significant role in diverse and distinct biological functions. Among these, myoglobin and hemoglobin, the tertiary and quaternary protein, are the most popular of the hemoproteins that respectively store and transport of oxygen in mammals. Functions of the proteins are differently performed through the dynamics of proteins in the aqueous solution, which strongly affected by the environmental conditions and temperatures. The difference in the protein structure is expected to have distinctive dynamics in the aqueous environment. Employing the high sensitive megahertz to terahertz dielectric spectroscopy, we are able to collect the complex dielectric response of each solution, analyze the dynamics of the proteins and the hydration shells. Temperature is varied during the experimental study to clarify the effect of temperature on protein functions and dynamics. The results help us to identify the dynamics of the hemeproteins and protein-water interaction that determine biochemical functions and reactivity of proteins. |
Tuesday, March 16, 2021 8:24AM - 8:36AM Live |
E12.00003: Investigation of Electrical Conductance in Immobilized Zebrafish Cryptochrome (zfCRY4) Protein Anh Nguyen, Carrie Partch, David Lederman In the past decades, several studies have shown that many animals, especially migratory birds, have an ability to detect and utilize the Earth’s magnetic field information to navigate their way during migration. A magnetic sensing mechanism is believed to be located in the bird's eyes which relies on protein cryptochrome proteins (CRYs). This protein belongs to a class of flavoproteins and is sensitive to blue light. The signaling state of cryptochrome is controlled by the oxidation state of flavin adenine dinucleotide (FAD), which can be activated via a coherent photoreduction process. Furthermore, the behavior of electron hopping in the FAD cofactor is theoretically known to depend on the presence of an external magnetic field. Immobilized zebrafish (Danio rerio) cryptochrome 4 (zfCRY4) protein on an ultra-flat gold thin film was studied to investigate the potential implementation in future devices. Results will be presented on the electrical conductance of a single protein thin film measured with conductive atomic force microscopy (C-AFM) as a function of tip force and blue light illumination. |
Tuesday, March 16, 2021 8:36AM - 8:48AM Live |
E12.00004: Computational Studies of Asymmetric Conformational Dynamics of AAA+ Machines Involved in Protein Disaggregation Ashan Dayananda, Ruxandra I Dima, George N Stan Caseinolytic (Clp) ATPases are AAA+ (ATPases associated with diverse cellular Activities) biological nanomachines that assist essential quality control processes of protein degradation or disaggregation. ClpB is a double-ring hexamer that resolubilizes protein aggregates in repetitive cycles of non-concerted conformational transitions coupled with mechanical forces applied by pore loops onto substrate proteins. To study the allosteric regulation and asymmetric conformational dynamics of this machine, we performed all-atom molecular dynamics simulations of two different conformational states (“ring” and “spiral”) of ClpB in nucleotide and/or substrate-bound or apo configurations. Simulation results highlight distinct mechanisms of dynamic stabilization of rings formed by two nucleotide binding domains (NBDs) of ClpB. Whereas the network of salt bridges stabilizing the NBD1 ring involves the canonical loops, in accord with experimental data, that of NBD2 involves non-canonical loops. Using machine learning approaches, we find that strong intra-ring collaboration involves correlated motions of NBD domains. Analysis of relaxation dynamics of canonical loops indicates coupling of local and collective motions on time scales consistent with experimental results. |
Tuesday, March 16, 2021 8:48AM - 9:00AM Live |
E12.00005: A Comparison of the Slow Dynamics in the Protein Ubiquitin Predicted by the LE4PD, PCA, and tICA from a Long Equilibrium Molecular Dynamics Simulation Eric Beyerle, Marina Giuseppina Guenza The Langevin Equation for Protein Dynamics (LE4PD) is a coarse-grained diffusive method to model protein dynamics, accounting for hydrodynamic effects and mode-dependent free-energy barriers. The LE4PD has been used to quantify the dynamics of proteins on timescales ranging from the picosecond to tens of nanoseconds. Here, we connect the slow dynamics predicted by the LE4PD to that predicted by principal component analysis (PCA) and time-lagged component analysis (tICA). An analytic connection between the LE4PD and PCA is made, while the comparison between the LE4PD and tICA is qualitative. Performing this comparison for a microsecond molecular dynamics trajectory of the protein ubiquitin, we find all three methods predict slow dynamics in three main regions of the protein (the Lys11 and 50 s loops and C-terminal tail), but the decomposition of the dynamics can differ significantly. The tICA finds the slowest motions are due to fluctuations in the 50 s loop, a result supported by the LE4PD once free-energy barriers are included in the analysis. We also find that inclusion of free-energy barriers and hydrodynamic interactions affects greatly the predicted LE4PD dynamics when compared to PCA. |
Tuesday, March 16, 2021 9:00AM - 9:12AM Live |
E12.00006: Combining Consensus and Ensemble Docking Methods Improves Molecular Docking Connor Morris, Brenden Stark, Dennis Della Corte Molecular docking programs are computational tools used to predict protein-ligand binding poses and energy. They are widely used in drug discovery to filter binding ligands from nonbinding ones in the search for potential drug candidates. However, they suffer from two main weaknesses: inaccurate scoring functions and rigid protein receptors. Two distinct methods, consensus docking and ensemble docking, are used to account for these problems separately. Consensus docking uses multiple docking scoring functions to evaluate docking poses, mitigating the weaknesses of each individual scoring function. Ensemble docking uses molecular dynamics (MD) to incorporate protein flexibility into docking simulations. We present a combined consensus and ensemble docking protocol to further improve docking predictions. |
Tuesday, March 16, 2021 9:12AM - 9:48AM Not Participating |
E12.00007: TBD Invited Speaker: Ruth Nussinov 2020 APS Fellow |
Tuesday, March 16, 2021 9:48AM - 10:00AM Live |
E12.00008: Binding mechanism of SARS-CoV-2 spike protein with human ACE2 receptor Rajendra Koirala, Bidhya Thapa, Shyam Khanal, Jhulan Powrel, Rajendra P Adhikari, Narayan Adhikari SARS-CoV-2 virus interacts via Cterminal domain of spike protein to human cell receptor protein hACE2.Amino acid residues residing at the interface play vital role in binding of SARS-CoV-2 CTD to hACE2.The detailed atomic level investigation of interactions at binding interface of SARS-CoV-2CTD hACE2 provides indispensable information on better understanding of location for drug target. In the present work, we have studied the dynamical behaviour of the complex by analyzing the molecular dynamics (MD) trajectories.The major interacting residues of SARS-CoV-2CTD and hACE2 have been identified by analyzing the nonbonded interactions such as hydrogen bondings, salt bridges, hydrophobic interactions, van der Waals interactions etc. Umbrella sampling method has been used to estimate the binding free energy for in-depth understanding of binding mechanism between virus protein and host receptor. The binding free energy difference, key residues at the interface,important atomic interactions and contact surface areas have been compared with the molecular complex of SARSCoV and hACE2. Relatively larger contact surface area, more non-bonded interactions as well as greater binding free energy provide the evidence for favorable binding of SARSCoV-2 with hACE2 receptor than SARS-CoV. |
Tuesday, March 16, 2021 10:00AM - 10:12AM Live |
E12.00009: Flow sensing in the bacterial flagellar motor of E. Coli Faris Sinjab, Ekaterina Krasnopeeva, Jerko Rosko, Teuta Pilizota E. coli swims by rotating several flagella randomly distributed along the cell body. At the base of each flagellum is the bacterial flagellar motor, a rotary molecular protein complex that couples the proton motive force to the rotation of flagellar filaments, which has been of interest to scientists for several decades. Membrane bound proteins, called chemo-sensors, can sense various environmental signals and activate a signalling cascade that influences motor rotation. Together, these components comprise the chemotactic network. Recently, it has been demonstrated that the motor is not only an output of a sensory response but also a sensor itself. It can modulate its speed and direction of rotation in response to mechanical stimuli, specifically changes in the motor torque. We show that the motor is able to respond to changes in the shear flow, which is likely related to torque-sensitive mechanosensing. We are characterising this response by varying the flow speed and adjusting the availability of torque-generating stator proteins, and modifying some recent biophysical models to explore possible shear flow sensing mechanisms. These results provide insight into how E. coli navigate complex environments, but may also enable the use of the motor as a flow sensor. |
Tuesday, March 16, 2021 10:12AM - 10:24AM Live |
E12.00010: Coarse-grained model of dielectric geometry-modified screened electrostatic protein-protein interactions Joshua Dickie, David S. Ross, John Hamilton, Christopher W. Wahle, George Thurston To refine a coarse-grained model of protein interactions, we seek to conveniently represent how dielectric interface geometry and charge placement affect screened aqueous electrostatic interactions. We study two neighboring spheres with near-surface charges, for which we solve the linearized Poisson-Boltzmann equation as a function of sphere-sphere separation. The spheres have 15 Angstrom diameters and internal static dielectric coefficients of 3, and the solvent Debye length is 6 Angstroms; parameters consistent with our charge-regulation model of bovine gamma-B crystallin. The screened electrostatic potential resulting from a single charge can be 4 to 6 times as strong as an unmodified Debye-Huckel screened potential, depending on sphere separation. For a fixed on- or off-axis charge in the first sphere, the two-dimensional angular dependence of the near-surface potential in the second sphere is well-modeled by a rotated, possibly off-center Student t-distribution at each sphere-sphere distance. We combine these results with dispersion interactions to model the orientation-dependent protein-protein potential for two gamma crystallins with multiple, charge-regulated amino-acid residues sited in accordance with their crystal structures. |
Tuesday, March 16, 2021 10:24AM - 10:36AM Live |
E12.00011: van der Waals Forces in Biomolecular Systems: from Solvation to Long-range Interaction Mechanisms Martin Stoehr, Matteo Gori, Philip Kurian, Alexandre Tkatchenko One decisive characteristic of the biomolecular machinery is the access to a rich set of well-defined, coordinated processes. Most of these processes involve collective conformational changes and occur in an aqueous environment. Conformational changes of (bio)molecules as well as their interaction with water are thereby largely governed by non-covalent van der Waals (vdW) dispersion interactions. By virtue of their intrinsically collective nature, vdW forces also represent a key factor for collective nuclear behavior. Our understanding of intra- and intermolecular response and vdW interaction in complex (bio)molecular systems, however, is still rather limited. Here, we investigate the electronic response properties and vdW interaction in biomolecular systems within a quantum-mechanical many-body treatment. In particular, we analyze the non-local reponse of solvated proteins and highlight the role of beyond-pairwise vdW forces for protein stability and the protein-water interaction. We further examine the electronic behaviors in an enzyme-DNA complex from which the catalytically-active regions emerge as electronically-correlated domains. This phenomenon is proposed to form the basis of an efficient long-range interaction mechanism assisting biomolecular regulation and allostery. |
Tuesday, March 16, 2021 10:36AM - 10:48AM Live |
E12.00012: Electron transport through single proteins, peptides and amino acids Carlos Romero-Muñiz, María Ortega, Jose Guilherme Vilhena, Ismael Diéz-Pérez, Ruben Perez, Juan Carlos Cuevas, Linda Angela Zotti Proteins have proven to be promising candidates for molecular electronics, showing in some cases much higher conductance than one would naively expect from their size. In particular, the blue-copper azurin extracted from Pseudomonas aeruginosa has been the subject of many experimental studies, although the exact transport mechanism is still under debate. Here I will present our efforts towards understanding the origin of such interesting effects from a theoretical perspective, analyzing both the electronic structure and the geometrical arrangement [1-3]. In addition, I will discuss results obtained on the conductance of individual heptapeptides [4] and amino acids [5], which are the building blocks of proteins, as well on the electronic properties of junctions based on Cytochrome C [6]. |
Tuesday, March 16, 2021 10:48AM - 11:00AM On Demand |
E12.00013: Multi-Scale Computational Study on SARS-CoV and SARS-CoV-2 Yixin Xie, Lin Li The ongoing outbreak of COVID-19 has been a serious threat to human health worldwide. The virus SARS-CoV-2 initiates its infection to the human body via the interaction process of its spike (S) protein with the human Angiotensin-Converting Enzyme 2 (ACE2). Therefore, understanding the fundamental mechanisms of how S protein receptor binding domain (RBD) binds to ACE2 is essential for new treatments developments of COVID-19. Here we implemented multi-scale computational approaches to study the binding mechanisms of binding between ACE2 and S proteins of both SARS-CoV-2 and SARS-CoV. Electrostatic features of SARS-CoV and SARS-CoV-2 were calculated and compared. The results demonstrate that SARS-CoV and SARS-CoV-2 S proteins are both attractive to ACE2 by electrostatic forces even at difference distances. However, the residues contributing to the electrostatic features are quite different due to the mutations between SARS-CoV S protein and SARS-CoV-2 S protein. Key residues that are involved in salt bridges and hydrogen bonds are identified in this study, which may help the future drug design against COVID-19. |
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