Browsing by Subject "Crystallization"
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Item Open Access Characterizing protein crystal contacts and their role in crystallization: rubredoxin as a case study.(Soft Matter, 2014-01-14) Fusco, Diana; Headd, Jeffrey J; De Simone, Alfonso; Wang, Jun; Charbonneau, PatrickThe fields of structural biology and soft matter have independently sought out fundamental principles to rationalize protein crystallization. Yet the conceptual differences and the limited overlap between the two disciplines have thus far prevented a comprehensive understanding of the phenomenon to emerge. We conduct a computational study of proteins from the rubredoxin family that bridges the two fields. Using atomistic simulations, we characterize the protein crystal contacts, and accordingly parameterize patchy particle models. Comparing the phase diagrams of these schematic models with experimental results enables us to critically examine the assumptions behind the two approaches. The study also reveals features of protein–protein interactions that can be leveraged to crystallize proteins more generally.Item Open Access Complex k band diagrams of 3D metamaterial/photonic crystals.(Opt Express, 2011-09-26) Fietz, Chris; Urzhumov, Yaroslav; Shvets, GennadyA finite element method (FEM) for solving a complex valued k(ω) vs. ω dispersion curve of a 3D metamaterial/photonic crystal system is presented. This 3D method is a generalization of a previously reported 2D eigenvalue method [Opt. Express 15, 9681 (2007)]. This method is particularly convenient for analyzing periodic systems containing dispersive (e.g., plasmonic) materials, for computing isofrequency surfaces in the k-space, and for calculating the decay length of the evanescent waves. Two specific examples are considered: a photonic crystal comprised of dielectric spheres and a plasmonic fishnet structure. Hybridization and avoided crossings between Mie resonances and propagating modes are numerically demonstrated. Negative index propagation of four electromagnetic modes distinguished by their symmetry is predicted for the plasmonic fishnets. By calculating the isofrequency contours, we also demonstrate that the fishnet structure is a hyperbolic medium.Item Open Access Computational crystallization.(Arch Biochem Biophys, 2016-07-15) Altan, Irem; Charbonneau, Patrick; Snell, Edward HCrystallization is a key step in macromolecular structure determination by crystallography. While a robust theoretical treatment of the process is available, due to the complexity of the system, the experimental process is still largely one of trial and error. In this article, efforts in the field are discussed together with a theoretical underpinning using a solubility phase diagram. Prior knowledge has been used to develop tools that computationally predict the crystallization outcome and define mutational approaches that enhance the likelihood of crystallization. For the most part these tools are based on binary outcomes (crystal or no crystal), and the full information contained in an assembly of crystallization screening experiments is lost. The potential of this additional information is illustrated by examples where new biological knowledge can be obtained and where a target can be sub-categorized to predict which class of reagents provides the crystallization driving force. Computational analysis of crystallization requires complete and correctly formatted data. While massive crystallization screening efforts are under way, the data available from many of these studies are sparse. The potential for this data and the steps needed to realize this potential are discussed.Item Open Access Computational Methods for RNA Structure Validation and Improvement.(Methods Enzymol, 2015) Jain, Swati; Richardson, David C; Richardson, Jane SWith increasing recognition of the roles RNA molecules and RNA/protein complexes play in an unexpected variety of biological processes, understanding of RNA structure-function relationships is of high current importance. To make clean biological interpretations from three-dimensional structures, it is imperative to have high-quality, accurate RNA crystal structures available, and the community has thoroughly embraced that goal. However, due to the many degrees of freedom inherent in RNA structure (especially for the backbone), it is a significant challenge to succeed in building accurate experimental models for RNA structures. This chapter describes the tools and techniques our research group and our collaborators have developed over the years to help RNA structural biologists both evaluate and achieve better accuracy. Expert analysis of large, high-resolution, quality-conscious RNA datasets provides the fundamental information that enables automated methods for robust and efficient error diagnosis in validating RNA structures at all resolutions. The even more crucial goal of correcting the diagnosed outliers has steadily developed toward highly effective, computationally based techniques. Automation enables solving complex issues in large RNA structures, but cannot circumvent the need for thoughtful examination of local details, and so we also provide some guidance for interpreting and acting on the results of current structure validation for RNA.Item Open Access Crystallization of asymmetric patchy models for globular proteins in solution.(Phys Rev E Stat Nonlin Soft Matter Phys, 2013-07) Fusco, Diana; Charbonneau, PatrickAsymmetric patchy particle models have recently been shown to describe the crystallization of small globular proteins with near-quantitative accuracy. Here, we investigate how asymmetry in patch geometry and bond energy generally impacts the phase diagram and nucleation dynamics of this family of soft matter models. We find the role of the geometry asymmetry to be weak, but the energy asymmetry to markedly interfere with the crystallization thermodynamics and kinetics. These results provide a rationale for the success and occasional failure of the proposal of George and Wilson for protein crystallization conditions as well as physical guidance for developing more effective protein crystallization strategies.Item Open Access Drug design from the cryptic inhibitor envelope.(Nat Commun, 2016-02-25) Lee, Chul-Jin; Liang, Xiaofei; Wu, Qinglin; Najeeb, Javaria; Zhao, Jinshi; Gopalaswamy, Ramesh; Titecat, Marie; Sebbane, Florent; Lemaitre, Nadine; Toone, Eric J; Zhou, PeiConformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC--an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target--access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics.Item Restricted Hard-sphere crystallization gets rarer with increasing dimension.(Phys Rev E Stat Nonlin Soft Matter Phys, 2009-12) van Meel, JA; Charbonneau, B; Fortini, A; Charbonneau, PWe recently found that crystallization of monodisperse hard spheres from the bulk fluid faces a much higher free-energy barrier in four than in three dimensions at equivalent supersaturation, due to the increased geometrical frustration between the simplex-based fluid order and the crystal [J. A. van Meel, D. Frenkel, and P. Charbonneau, Phys. Rev. E 79, 030201(R) (2009)]. Here, we analyze the microscopic contributions to the fluid-crystal interfacial free energy to understand how the barrier to crystallization changes with dimension. We find the barrier to grow with dimension and we identify the role of polydispersity in preventing crystal formation. The increased fluid stability allows us to study the jamming behavior in four, five, and six dimensions and to compare our observations with two recent theories [C. Song, P. Wang, and H. A. Makse, Nature (London) 453, 629 (2008); G. Parisi and F. Zamponi, Rev. Mod. Phys. (to be published)].Item Open Access Highly parallel acoustic assembly of microparticles into well-ordered colloidal crystallites.(Soft Matter, 2016-01-21) Owens, Crystal E; Shields, C Wyatt; Cruz, Daniela F; Charbonneau, Patrick; López, Gabriel PThe precise arrangement of microscopic objects is critical to the development of functional materials and ornately patterned surfaces. Here, we present an acoustics-based method for the rapid arrangement of microscopic particles into organized and programmable architectures, which are periodically spaced within a square assembly chamber. This macroscale device employs two-dimensional bulk acoustic standing waves to propel particles along the base of the chamber toward pressure nodes or antinodes, depending on the acoustic contrast factor of the particle, and is capable of simultaneously creating thousands of size-limited, isotropic and anisotropic assemblies within minutes. We pair experiments with Brownian dynamics simulations to model the migration kinetics and assembly patterns of spherical microparticles. We use these insights to predict and subsequently validate the onset of buckling of the assemblies into three-dimensional clusters by experiments upon increasing the acoustic pressure amplitude and the particle concentration. The simulations are also used to inform our experiments for the assembly of non-spherical particles, which are then recovered via fluid evaporation and directly inspected by electron microscopy. This method for assembly of particles offers several notable advantages over other approaches (e.g., magnetics, electrokinetics and optical tweezing) including simplicity, speed and scalability and can also be used in concert with other such approaches for enhancing the types of assemblies achievable.Item Open Access Learning about Biomolecular Solvation from Water in Protein Crystals.(The journal of physical chemistry. B, 2018-03) Altan, Irem; Fusco, Diana; Afonine, Pavel V; Charbonneau, PatrickWater occupies typically 50% of a protein crystal and thus significantly contributes to the diffraction signal in crystallography experiments. Separating its contribution from that of the protein is, however, challenging because most water molecules are not localized and are thus difficult to assign to specific density peaks. The intricateness of the protein-water interface compounds this difficulty. This information has, therefore, not often been used to study biomolecular solvation. Here, we develop a methodology to surmount in part this difficulty. More specifically, we compare the solvent structure obtained from diffraction data for which experimental phasing is available to that obtained from constrained molecular dynamics (MD) simulations. The resulting spatial density maps show that commonly used MD water models are only partially successful at reproducing the structural features of biomolecular solvation. The radial distribution of water is captured with only slightly higher accuracy than its angular distribution, and only a fraction of the water molecules assigned with high reliability to the crystal structure is recovered. These differences are likely due to shortcomings of both the water models and the protein force fields. Despite these limitations, we manage to infer protonation states of some of the side chains utilizing MD-derived densities.Item Embargo Melting and Glass Formation in Halide Perovskites(2024) Singh, AkashHalide perovskites represent a highly regarded class of optoelectronic semiconductors, demonstrating unprecedented performance in photovoltaic, light-emitting, and sensing devices. Despite their invention in 1892, almost exclusively, all the research (~50,000 publications) has focused on their crystalline state, characterized by precise atomic arrangements. Introducing controlled disorder through a melt and/or glassy state lacking significant long-range periodicity unlocks new avenues for applications, reminiscent of the transformative impact provided by glassy chalcogenides in commercial memory and computing applications. This dissertation introduces halide perovskites into the family of glass forming semiconductors, presenting various halide perovskites with adjustable melting, glass-forming, and glass-crystallization properties. These properties were thoroughly investigated using a comprehensive approach encompassing structural, thermal, mechanical, optoelectronic, spectroscopic, and numerical modeling techniques. The study highlights the principles involved in creating low-melting-temperature and switchable crystalline/glassy states, underscoring the critical importance of investigating these states for future applications in memory, computing, energy storage, reconfigurable metamaterials and photonic devices.
Item Open Access Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement.(Journal of nephrology, 2016-12) Gambaro, Giovanni; Croppi, Emanuele; Coe, Fredric; Lingeman, James; Moe, Orson; Worcester, Elen; Buchholz, Noor; Bushinsky, David; Curhan, Gary C; Ferraro, Pietro Manuel; Fuster, Daniel; Goldfarb, David S; Heilberg, Ita Pfeferman; Hess, Bernard; Lieske, John; Marangella, Martino; Milliner, Dawn; Preminger, Glen M; Reis Santos, Jose' Manuel; Sakhaee, Khashayar; Sarica, Kemal; Siener, Roswitha; Strazzullo, Pasquale; Williams, James C; Consensus Conference GroupBackground
Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research.Design
A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved.Results
Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients.Conclusions
This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.Item Open Access Purification, crystallization and preliminary X-ray diffraction studies of a complex between G protein-coupled receptor kinase 2 and Gbeta1gamma2.(Acta Crystallogr D Biol Crystallogr, 2003-05) Lodowski, David T; Barnhill, Jennifer F; Pitcher, Julie A; Capel, W Darrell; Lefkowitz, Robert J; Tesmer, John JGG protein-coupled receptor kinase 2 (GRK2) phosphorylates activated G protein-coupled receptors (GPCRs), which ultimately leads to their desensitization and/or downregulation. The enzyme is recruited to the plasma membrane via the interaction of its carboxyl-terminal pleckstrin-homology (PH) domain with the beta and gamma subunits of heterotrimeric G proteins (Gbetagamma). An improved purification scheme for GRK2 has been developed, conditions under which GRK2 forms a complex with Gbeta(1)gamma(2) have been determined and the complex has been crystallized in CHAPS detergent micelles. Crystals of the GRK2-Gbetagamma complex belong to space group C2 and have unit-cell parameters a = 187.0, b = 72.1, c = 122.0 A, beta = 115.2 degrees. A complete data set has been collected to 3.2 A resolution with Cu Kalpha radiation.Item Open Access Soft matter perspective on protein crystal assembly.(Colloids Surf B Biointerfaces, 2016-01-01) Fusco, Diana; Charbonneau, PatrickCrystallography may be the gold standard of protein structure determination, but obtaining the necessary high-quality crystals is also in some ways akin to prospecting for the precious metal. The tools and models developed in soft matter physics to understand colloidal assembly offer some insights into the problem of crystallizing proteins. This topical review describes the various analogies that have been made between proteins and colloids in that context. We highlight the explanatory power of patchy particle models, but also the challenges of providing guidance for crystallizing specific proteins. We conclude with a presentation of possible future research directions. This review is intended for soft matter scientists interested in protein crystallization as a self-assembly problem, and as an introduction to the pertinent physics literature for protein scientists more generally.