scholarly journals PDB_REDO: automated re-refinement of X-ray structure models in the PDB

2009 ◽  
Vol 42 (3) ◽  
pp. 376-384 ◽  
Author(s):  
Robbie P. Joosten ◽  
Jean Salzemann ◽  
Vincent Bloch ◽  
Heinz Stockinger ◽  
Ann-Charlott Berglund ◽  
...  
Keyword(s):  
Structural Biology ◽  
Large Scale ◽  
Homology Modelling ◽  
Three Dimensional ◽  
Data Bank ◽  
Rational Drug Design ◽  
X Ray ◽  
Rational Drug ◽  
Geometric Quality ◽  
Existing Structure

Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16 807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB_REDO databank (http://www.cmbi.ru.nl/pdb_redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour.

AGN torus threaded by large scale magnetic field

2018 ◽  
Vol 27 (10) ◽  
pp. 1844006
Author(s):  
A. Dorodnitsyn ◽  
T. Kallman
Keyword(s):  
Magnetic Field ◽  
Angular Momentum ◽  
Accretion Disk ◽  
Large Scale ◽  
Three Dimensional ◽  
X Ray ◽  
Radiative Feedback ◽  
Large Scale Magnetic Field ◽  
Three Dimensional Simulations

Large scale magnetic field can be easily dragged from galactic scales toward AGN along with accreting gas. There, it can contribute to both the formation of AGN “torus” and help to remove angular momentum from the gas which fuels AGN accretion disk. However the dynamics of such gas is also strongly influenced by the radiative feedback from the inner accretion disk. Here we present results from the three-dimensional simulations of pc-scale accretion which is exposed to intense X-ray heating.

scholarly journals Protein dynamics revealed by NMR relaxation methods

2018 ◽  
Vol 2 (1) ◽  
pp. 93-105 ◽  
Author(s):  
Fa-An Chao ◽  
R. Andrew Byrd
Keyword(s):  
Protein Dynamics ◽  
Structural Biology ◽  
Dynamic Models ◽  
Dimensional Space ◽  
Three Dimensional ◽  
Data Bank ◽  
Biological Macromolecules ◽  
Relaxation Methods ◽  
Genomic Databases ◽  
Wide Range

Structural biology often focuses primarily on three-dimensional structures of biological macromolecules, deposited in the Protein Data Bank (PDB). This resource is a remarkable entity for the worldwide scientific and medical communities, as well as the general public, as it is a growing translation into three-dimensional space of the vast information in genomic databases, e.g. GENBANK. There is, however, significantly more to understanding biological function than the three-dimensional co-ordinate space for ground-state structures of biomolecules. The vast array of biomolecules experiences natural dynamics, interconversion between multiple conformational states, and molecular recognition and allosteric events that play out on timescales ranging from picoseconds to seconds. This wide range of timescales demands ingenious and sophisticated experimental tools to sample and interpret these motions, thus enabling clearer insights into functional annotation of the PDB. NMR spectroscopy is unique in its ability to sample this range of timescales at atomic resolution and in physiologically relevant conditions using spin relaxation methods. The field is constantly expanding to provide new creative experiments, to yield more detailed coverage of timescales, and to broaden the power of interpretation and analysis methods. This review highlights the current state of the methodology and examines the extension of analysis tools for more complex experiments and dynamic models. The future for understanding protein dynamics is bright, and these extended tools bring greater compatibility with developments in computational molecular dynamics, all of which will further our understanding of biological molecular functions. These facets place NMR as a key component in integrated structural biology.

Structural biology and structure–function relationships of membrane proteins

2018 ◽  
Vol 47 (1) ◽  
pp. 47-61 ◽  
Author(s):  
Rosana Reis ◽  
Isabel Moraes
Keyword(s):  
Membrane Proteins ◽  
Structure Function ◽  
Structural Biology ◽  
Drug Targets ◽  
Three Dimensional ◽  
Data Bank ◽  
Technical Advances ◽  
Medical Importance ◽  
G Protein Coupled ◽  
Important Drug

Abstract The study of structure–function relationships of membrane proteins (MPs) has been one of the major goals in the field of structural biology. Many Noble Prizes regarding remarkable accomplishments in MP structure determination and biochemistry have been awarded over the last few decades. Mutations or improper folding of these proteins are associated with numerous serious illnesses. Therefore, as important drug targets, the study of their primary sequence and three-dimensional fold, combined with cell-based assays, provides vital information about their structure–function relationships. Today, this information is vital to drug discovery and medicine. In the last two decades, many have been the technical advances and breakthroughs in the field of MP structural biology that have contributed to an exponential growth in the number of unique MP structures in the Protein Data Bank. Nevertheless, given the medical importance and many unanswered questions, it will never be an excess of MP structures, regardless of the method used. Owing to the extension of the field, in this brief review, we will only focus on structure–function relationships of the three most significant pharmaceutical classes: G protein-coupled receptors, ion channels and transporters.

scholarly journals xMDFF: molecular dynamics flexible fitting of low-resolution X-ray structures

2014 ◽  
Vol 70 (9) ◽  
pp. 2344-2355 ◽  
Author(s):  
Ryan McGreevy ◽  
Abhishek Singharoy ◽  
Qufei Li ◽  
Jingfen Zhang ◽  
Dong Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Large Scale ◽  
Protein Structures ◽  
Data Bank ◽  
Real Space ◽  
Low Resolution ◽  
X Ray ◽  
X Ray Crystallography ◽  
Atomic Structures ◽  
Electron Density Map

X-ray crystallography remains the most dominant method for solving atomic structures. However, for relatively large systems, the availability of only medium-to-low-resolution diffraction data often limits the determination of all-atom details. A new molecular dynamics flexible fitting (MDFF)-based approach, xMDFF, for determining structures from such low-resolution crystallographic data is reported. xMDFF employs a real-space refinement scheme that flexibly fits atomic models into an iteratively updating electron-density map. It addresses significant large-scale deformations of the initial model to fit the low-resolution density, as tested with synthetic low-resolution maps of D-ribose-binding protein. xMDFF has been successfully applied to re-refine six low-resolution protein structures of varying sizes that had already been submitted to the Protein Data Bank. Finally,viasystematic refinement of a series of data from 3.6 to 7 Å resolution, xMDFF refinements together with electrophysiology experiments were used to validate the first all-atom structure of the voltage-sensing protein Ci-VSP.

Rational Drug Design Using Integrative Structural Biology

2018 ◽  
pp. 89-111 ◽  
Author(s):  
Magda S. Chegkazi ◽  
Michael Mamais ◽  
Anastasia I. Sotiropoulou ◽  
Evangelia D. Chrysina
Keyword(s):  
Drug Design ◽  
Structural Biology ◽  
Rational Drug Design ◽  
Rational Drug ◽  
Integrative Structural Biology

scholarly journals Universal Architectural Concepts Underlying Protein Folding Patterns

2021 ◽  
Vol 7 ◽  
Author(s):  
Arun S. Konagurthu ◽  
Ramanan Subramanian ◽  
Lloyd Allison ◽  
David Abramson ◽  
Peter J. Stuckey ◽  
...  
Keyword(s):  
Structure Prediction ◽  
Protein Structures ◽  
Data Bank ◽  
Rational Drug Design ◽  
Basis Set ◽  
Sequence Structure ◽  
Information Theoretic ◽  
Protein Architecture ◽  
Structure Correlations ◽  
Rational Drug

What is the architectural “basis set” of the observed universe of protein structures? Using information-theoretic inference, we answer this question with a dictionary of 1,493 substructures—called concepts—typically at a subdomain level, based on an unbiased subset of known protein structures. Each concept represents a topologically conserved assembly of helices and strands that make contact. Any protein structure can be dissected into instances of concepts from this dictionary. We dissected the Protein Data Bank and completely inventoried all the concept instances. This yields many insights, including correlations between concepts and catalytic activities or binding sites, useful for rational drug design; local amino-acid sequence–structure correlations, useful for ab initio structure prediction methods; and information supporting the recognition and exploration of evolutionary relationships, useful for structural studies. An interactive site, Proçodic, at http://lcb.infotech.monash.edu.au/prosodic (click), provides access to and navigation of the entire dictionary of concepts and their usages, and all associated information. This report is part of a continuing programme with the goal of elucidating fundamental principles of protein architecture, in the spirit of the work of Cyrus Chothia.

scholarly journals A pharmacological master key mechanism that unlocks the selectivity filter gate in K+channels

Science ◽  
2019 ◽  
Vol 363 (6429) ◽  
pp. 875-880 ◽  
Author(s):  
Marcus Schewe ◽  
Han Sun ◽  
Ümit Mert ◽  
Alexandra Mackenzie ◽  
Ashley C. W. Pike ◽  
...  
Keyword(s):  
Selectivity Filter ◽  
Rational Drug Design ◽  
Related Gene ◽  
K Channels ◽  
X Ray ◽  
Voltage Gated ◽  
X Ray Crystallography ◽  
Rational Drug ◽  
Dynamics Simulations ◽  
Pore Domain

Potassium (K+) channels have been evolutionarily tuned for activation by diverse biological stimuli, and pharmacological activation is thought to target these specific gating mechanisms. Here we report a class of negatively charged activators (NCAs) that bypass the specific mechanisms but act as master keys to open K+channels gated at their selectivity filter (SF), including many two-pore domain K+(K2P) channels, voltage-gated hERG (human ether-à-go-go–related gene) channels and calcium (Ca2+)–activated big-conductance potassium (BK)–type channels. Functional analysis, x-ray crystallography, and molecular dynamics simulations revealed that the NCAs bind to similar sites below the SF, increase pore and SF K+occupancy, and open the filter gate. These results uncover an unrecognized polypharmacology among K+channel activators and highlight a filter gating machinery that is conserved across different families of K+channels with implications for rational drug design.

MLDB: macromolecule ligand database

2009 ◽  
Vol 43 (1) ◽  
pp. 200-202 ◽  
Author(s):  
S. E. Saravanan ◽  
R. Karthi ◽  
K. Sathish ◽  
K. Kokila ◽  
R. Sabarinathan ◽  
...  
Keyword(s):  
Protein Data Bank ◽  
Structural Biology ◽  
Scientific Community ◽  
Three Dimensional ◽  
Data Bank

MLDB (macromolecule ligand database) is a knowledgebase containing ligands co-crystallized with the three-dimensional structures available in the Protein Data Bank. The proposed knowledgebase serves as an open resource for the analysis and visualization of all ligands and their interactions with macromolecular structures. MLDB can be used to search ligands, and their interactions can be visualized both in text and graphical formats. MLDB will be updated at regular intervals (weekly) with automated Perl scripts. The knowledgebase is intended to serve the scientific community working in the areas of molecular and structural biology. It is available free to users around the clock and can be accessed at http://dicsoft2.physics.iisc.ernet.in/mldb/.

Antimalarial Drug Discovery: In Silico Structural Biology and Rational Drug Design

2009 ◽  
Vol 9 (3) ◽  
pp. 304-318 ◽  
Author(s):  
TAP de Beer ◽  
GA Wells ◽  
PB Burger ◽  
F. Joubert ◽  
E. Marechal ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Drug Design ◽  
Structural Biology ◽  
Antimalarial Drug ◽  
In Silico ◽  
Rational Drug Design ◽  
Rational Drug

scholarly journals Identifying, studying and making good use of macromolecular crystals

2014 ◽  
Vol 70 (8) ◽  
pp. 993-1008 ◽  
Author(s):  
Guillermo Calero ◽  
Aina E. Cohen ◽  
Joseph R. Luft ◽  
Janet Newman ◽  
Edward H. Snell
Keyword(s):  
Data Collection ◽  
Visible Light ◽  
Structural Biology ◽  
Protein Structures ◽  
Data Bank ◽  
Potential Outcomes ◽  
Structural Knowledge ◽  
X Ray ◽  
X Ray Crystallography ◽  
Molecular Scale

Structural biology has contributed tremendous knowledge to the understanding of life on the molecular scale. The Protein Data Bank, a depository of this structural knowledge, currently contains over 100 000 protein structures, with the majority stemming from X-ray crystallography. As the name might suggest, crystallography requires crystals. As detectors become more sensitive and X-ray sources more intense, the notion of a crystal is gradually changing from one large enough to embellish expensive jewellery to objects that have external dimensions of the order of the wavelength of visible light. Identifying these crystals is a prerequisite to their study. This paper discusses developments in identifying these crystals during crystallization screening and distinguishing them from other potential outcomes. The practical aspects of ensuring that once a crystal is identified it can then be positioned in the X-ray beam for data collection are also addressed.

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