scholarly journals An Open Source Mesh Generation Platform for Biophysical Modeling Using Realistic Cellular Geometries

2019 ◽  
Author(s):  
Christopher T. Lee ◽  
Justin G. Laughlin ◽  
John B. Moody ◽  
Rommie E. Amaro ◽  
J. Andrew McCammon ◽  
...  
Keyword(s):  
Structural Biology ◽  
Mesh Generation ◽  
Structural Information ◽  
Electron Tomography ◽  
Structural Data ◽  
Biophysical Modeling ◽  
X Ray Crystallography ◽  
Biophysical Models ◽  
Geometric Mesh ◽  
And Mathematics

ABSTRACTAdvances in imaging methods such as electron microscopy, tomography, and other modalities are enabling high-resolution reconstructions of cellular and organelle geometries. Such advances pave the way for using these geometries for biophysical and mathematical modeling once these data can be represented as a geometric mesh, which, when carefully conditioned, enables the discretization and solution of partial differential equations. In this study, we outline the steps for a naïve user to approach GAMer 2, a mesh generation code written in C++ designed to convert structural datasets to realistic geometric meshes, while preserving the underlying shapes. We present two example cases, 1) mesh generation at the subcellular scale as informed by electron tomography, and 2) meshing a protein with structure from x-ray crystallography. We further demonstrate that the meshes generated by GAMer are suitable for use with numerical methods. Together, this collection of libraries and tools simplifies the process of constructing realistic geometric meshes from structural biology data.SIGNIFICANCEAs biophysical structure determination methods improve, the rate of new structural data is increasing. New methods that allow the interpretation, analysis, and reuse of such structural information will thus take on commensurate importance. In particular, geometric meshes, such as those commonly used in graphics and mathematics, can enable a myriad of mathematical analysis. In this work, we describe GAMer 2, a mesh generation library designed for biological datasets. Using GAMer 2 and associated tools PyGAMer and BlendGAMer, biologists can robustly generate computer and algorithm friendly geometric mesh representations informed by structural biology data. We expect that GAMer 2 will be a valuable tool to bring realistic geometries to biophysical models.

Introduction

2018 ◽  
Author(s):  
Eaton E. Lattman ◽  
Thomas D. Grant ◽  
Edward H. Snell
Keyword(s):  
Structural Biology ◽  
Single Molecule ◽  
Small Angle ◽  
Structural Information ◽  
Complementary Technique ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Future ◽  
The Relationship ◽  
Basic Level

This chapter provides an introduction to small angle solution scattering with particular reference to the complementary technique of X-ray crystallography and the relationship between the two. It describes at its most basic level the theoretical underpinnings of solution scattering starting from a single molecule and how this information is sampled in crystals versus in solution. A brief introduction is given to some of the primary types of structural information that can be obtained from experiments. The chapter concludes discussing some of the most common applications of the technique in structural biology, and where the future is likely headed.

Structural Analysis of Proteins on Lipid Substrates

2000 ◽  
Vol 6 (S2) ◽  
pp. 1182-1183
Author(s):  
Elizabeth M. Wilson-Kubalek
Keyword(s):  
Structural Information ◽  
Rapid Determination ◽  
3D Structure ◽  
Three Dimensional ◽  
Molecular Complexes ◽  
Structural Data ◽  
X Ray Crystallography ◽  
Helical Protein ◽  
3D Structure Determination

Electron microscopy (EM) has become an increasingly powerful method for the determination of three-dimensional (3D) structures of proteins and macromolecular complexes. EM offers advantages over X-ray crystallography and NMR for obtaining structural information about proteins in physiological conditions, as components of large assemblies, that cannot be obtained in large quantity, or that fail to yield 3D crystals. EM has been used to obtain structural data from images of isolated molecules and molecular complexes, two-dimensional (2D) protein crystals, and helical protein arrays. Helically arranged proteins allow the most rapid determination of 3D maps because they contain a complete range of equally spaced molecular views, therefore no tilting of the sample with respect to the electron beam is required. However, so far 3D structure determination of helical assemblies has been limited to proteins that naturally adopt this organization and to proteins that fortuitously crystallize as helices.

scholarly journals Structural and functional characterization of the intracellular filament-forming nitrite oxidoreductase multiprotein complex

2021 ◽  
Author(s):  
Tadeo Moreno Chicano ◽  
Lea Dietrich ◽  
Naomi M. de Almeida ◽  
Mohd. Akram ◽  
Elisabeth Hartmann ◽  
...  
Keyword(s):  
Structural Information ◽  
Electron Tomography ◽  
Functional Characterization ◽  
Anammox Bacteria ◽  
Multiprotein Complex ◽  
Tubule Formation ◽  
X Ray Crystallography ◽  
Helical Reconstruction ◽  
Nitrite Oxidizing Bacteria ◽  
Nitrite Oxidoreductase

AbstractNitrate is an abundant nutrient and electron acceptor throughout Earth’s biosphere. Virtually all nitrate in nature is produced by the oxidation of nitrite by the nitrite oxidoreductase (NXR) multiprotein complex. NXR is a crucial enzyme in the global biological nitrogen cycle, and is found in nitrite-oxidizing bacteria (including comammox organisms), which generate the bulk of the nitrate in the environment, and in anaerobic ammonium-oxidizing (anammox) bacteria which produce half of the dinitrogen gas in our atmosphere. However, despite its central role in biology and decades of intense study, no structural information on NXR is available. Here, we present a structural and biochemical analysis of the NXR from the anammox bacterium Kuenenia stuttgartiensis, integrating X-ray crystallography, cryo-electron tomography, helical reconstruction cryo-electron microscopy, interaction and reconstitution studies and enzyme kinetics. We find that NXR catalyses both nitrite oxidation and nitrate reduction, and show that in the cell, NXR is arranged in tubules several hundred nanometres long. We reveal the tubule architecture and show that tubule formation is induced by a previously unidentified, haem-containing subunit, NXR-T. The results also reveal unexpected features in the active site of the enzyme, an unusual cofactor coordination in the protein’s electron transport chain, and elucidate the electron transfer pathways within the complex.

scholarly journals In crystallo optical spectroscopy as a complementary tool to crystallography

2014 ◽  
Vol 70 (a1) ◽  
pp. C1530-C1530
Author(s):  
Antoine Royant
Keyword(s):  
Structural Biology ◽  
Structural Data ◽  
Portable Devices ◽  
X Ray Crystallography ◽  
The Status ◽  
On Line ◽  
Complementary Techniques ◽  
Year 2000 ◽  
Scientific Questions ◽  
Biology Group

The analysis of structural data obtained by X-ray crystallography benefits from information obtained from complementary techniques, especially if these are applied to the crystals themselves. As a consequence, optical spectroscopies as applied in Structural Biology have become instrumental in assessing the relevance of many crystallographic results. Since the year 2000, such data can be recorded close to, or directly on, the Structural Biology Group beamlines of the ESRF. A core laboratory featuring various spectrometers, named the Cryobench, is now in its third version and houses portable devices that can be directly mounted on beamlines. This presentation will report the status of the current version of the Cryobench, now located on the MAD beamline ID29 and thus called ID29S-Cryobench, S standing for 'Spectroscopy'. In particular, the new on-line Raman data collection mode of ID29 will be described. Finally, it will review the diverse experiments that can be performed at the Cryobench, highlighting various scientific questions that can be addressed.

scholarly journals Raman optical activity: A new light on proteins, carbohydrates and glycoproteins

2006 ◽  
Vol 28 (3) ◽  
pp. 27-31 ◽  
Author(s):  
Laurence D. Barron
Keyword(s):  
Structural Biology ◽  
Optical Activity ◽  
Large Range ◽  
Structural Information ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
The Novel ◽  
X Ray ◽  
X Ray Crystallography ◽  
Raman Optical Activity

The core techniques of structural biology, namely X-ray crystallography and multidimensional NMR, are often not applicable to many important samples due to fundamental experimental problems, such as the lack of suitable crystals in the X-ray case or excessive size or flexibility for NMR. Carbohydrates and glycoproteins are especially challenging in this respect. The novel technique of vibrational ROA (Raman optical activity), which combines the advantages of vibrational spectroscopy with the extra sensitivity to three-dimensional structure of chiroptical methods such as CD (circular dichroism), has much promise for studying a large range of biomolecules, from the smallest to the largest, in aqueous solution. Among other things, it is capable of providing structural information about both the polypeptide and the carbohydrate structure of intact glycoproteins and should become an indispensable spectroscopy tool for glycobiology.

scholarly journals Analysis of the Quality of Macromolecular Structures

2017 ◽  
Author(s):  
Dinakar M. Salunke
Keyword(s):  
Structural Biology ◽  
Model Building ◽  
Structural Data ◽  
Data Bank ◽  
X Ray Crystallography ◽  
Structure Factors ◽  
Scientific Systems ◽  
Published Research

AbstractStructure determination utilizing X-ray crystallography involves collection of diffraction data, determination of initial phases followed by iterative rounds of model building and crystallographic refinement to improve the phases and minimize the differences between calculated and observed structure factors. At each of these stages, a variety of statistical filters exist to ensure appropriate validation. Biologically important observations often come from interpretations of signals that need to be carefully deciphered from noise and therefore human intervention is as important as the automated filters. Currently, all structural data are deposited in the Protein Data Bank and this repository is continuously evolving to incorporate possible new improvements in macromolecular crystallography. The journals that publish data arising from structural studies modulate their policies to take cognizance of new improved methodologies. The PDB and journals have evolved an accepted protocol to ensure the integrity of crystallographic results. As a result, the quality of available data and interpretations are becoming better over the years. However, there have been periodic efforts by some individuals who misuse validation mechanisms to selectively target published research through spurious challenges. These actions do more harm to the field of structural biology and runs counter to their claim to cleanse the system. The scientific systems in structural biology are robust and capable of self-correction and unwarranted vigilantism is counterproductive.

scholarly journals In crystallooptical spectroscopy (icOS) as a complementary tool on the macromolecular crystallography beamlines of the ESRF

2015 ◽  
Vol 71 (1) ◽  
pp. 15-26 ◽  
Author(s):  
David von Stetten ◽  
Thierry Giraud ◽  
Philippe Carpentier ◽  
Franc Sever ◽  
Maxime Terrien ◽  
...  
Keyword(s):  
Structural Biology ◽  
Structural Data ◽  
Current Status ◽  
Portable Devices ◽  
X Ray ◽  
X Ray Crystallography ◽  
Complementary Techniques ◽  
Year 2000 ◽  
Scientific Questions ◽  
Biology Group

The analysis of structural data obtained by X-ray crystallography benefits from information obtained from complementary techniques, especially as applied to the crystals themselves. As a consequence, optical spectroscopies in structural biology have become instrumental in assessing the relevance and context of many crystallographic results. Since the year 2000, it has been possible to record such data adjacent to, or directly on, the Structural Biology Group beamlines of the ESRF. A core laboratory featuring various spectrometers, named the Cryobench, is now in its third version and houses portable devices that can be directly mounted on beamlines. This paper reports the current status of the Cryobench, which is now located on the MAD beamline ID29 and is thus called the ID29S-Cryobench (where S stands for `spectroscopy'). It also reviews the diverse experiments that can be performed at the Cryobench, highlighting the various scientific questions that can be addressed.

Biophysical applications in structural and molecular biology

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Solomon Tsegaye ◽  
Gobena Dedefo ◽  
Mohammed Mehdi
Keyword(s):  
Structural Biology ◽  
Structural Information ◽  
Conformational Dynamics ◽  
Biological Macromolecules ◽  
X Ray Diffraction ◽  
Biological Mechanisms ◽  
X Ray ◽  
X Ray Crystallography ◽  
Cryo Electron Microscopy ◽  
Biophysical Techniques

Abstract The main objective of structural biology is to model proteins and other biological macromolecules and link the structural information to function and dynamics. The biological functions of protein molecules and nucleic acids are inherently dependent on their conformational dynamics. Imaging of individual molecules and their dynamic characteristics is an ample source of knowledge that brings new insights about mechanisms of action. The atomic-resolution structural information on most of the biomolecules has been solved by biophysical techniques; either by X-ray diffraction in single crystals or by nuclear magnetic resonance (NMR) spectroscopy in solution. Cryo-electron microscopy (cryo-EM) is emerging as a new tool for analysis of a larger macromolecule that couldn’t be solved by X-ray crystallography or NMR. Now a day’s low-resolution Cryo-EM is used in combination with either X-ray crystallography or NMR. The present review intends to provide updated information on applications like X-ray crystallography, cryo-EM and NMR which can be used independently and/or together in solving structures of biological macromolecules for our full comprehension of their biological mechanisms.

Automated electron tomography: from data collection to image processing

1995 ◽  
Vol 53 ◽  
pp. 26-27
Author(s):  
Weiping Liu ◽  
Jennifer Fung ◽  
W.J. de Ruijter ◽  
Hans Chen ◽  
John W. Sedat ◽  
...  
Keyword(s):  
Image Processing ◽  
Data Collection ◽  
Structural Information ◽  
Imaging Technique ◽  
Electron Tomography ◽  
Ccd Camera ◽  
Automated Data Collection ◽  
Full Control ◽  
Transmission Electron ◽  
Amorphous Structures

Electron tomography is a technique where many projections of an object are collected from the transmission electron microscope (TEM), and are then used to reconstruct the object in its entirety, allowing internal structure to be viewed. As vital as is the 3-D structural information and with no other 3-D imaging technique to compete in its resolution range, electron tomography of amorphous structures has been exercised only sporadically over the last ten years. Its general lack of popularity can be attributed to the tediousness of the entire process starting from the data collection, image processing for reconstruction, and extending to the 3-D image analysis. We have been investing effort to automate all aspects of electron tomography. Our systems of data collection and tomographic image processing will be briefly described.To date, we have developed a second generation automated data collection system based on an SGI workstation (Fig. 1) (The previous version used a micro VAX). The computer takes full control of the microscope operations with its graphical menu driven environment. This is made possible by the direct digital recording of images using the CCD camera.

scholarly journals Integrating genome sequence and structural data for statistical learning to predict transcription factor binding sites

2020 ◽  
Vol 48 (22) ◽  
pp. 12604-12617
Author(s):  
Pengpeng Long ◽  
Lu Zhang ◽  
Bin Huang ◽  
Quan Chen ◽  
Haiyan Liu
Keyword(s):  
Genome Sequence ◽  
Energy Function ◽  
Structural Information ◽  
Structural Data ◽  
P Values ◽  
A Genome ◽  
Z Scores ◽  
Transcription Regulators ◽  
Dna Specificity ◽  
Tetracycline Repressor

Abstract We report an approach to predict DNA specificity of the tetracycline repressor (TetR) family transcription regulators (TFRs). First, a genome sequence-based method was streamlined with quantitative P-values defined to filter out reliable predictions. Then, a framework was introduced to incorporate structural data and to train a statistical energy function to score the pairing between TFR and TFR binding site (TFBS) based on sequences. The predictions benchmarked against experiments, TFBSs for 29 out of 30 TFRs were correctly predicted by either the genome sequence-based or the statistical energy-based method. Using P-values or Z-scores as indicators, we estimate that 59.6% of TFRs are covered with relatively reliable predictions by at least one of the two methods, while only 28.7% are covered by the genome sequence-based method alone. Our approach predicts a large number of new TFBs which cannot be correctly retrieved from public databases such as FootprintDB. High-throughput experimental assays suggest that the statistical energy can model the TFBSs of a significant number of TFRs reliably. Thus the energy function may be applied to explore for new TFBSs in respective genomes. It is possible to extend our approach to other transcriptional factor families with sufficient structural information.

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