scholarly journals Ranking Enzyme Structures in the PDB by Bound Ligand Similarity to Biological Substrates

Structure ◽  
2018 ◽  
Vol 26 (4) ◽  
pp. 565-571.e3 ◽  
Author(s):  
Jonathan D. Tyzack ◽  
Laurent Fernando ◽  
Antonio J.M. Ribeiro ◽  
Neera Borkakoti ◽  
Janet M. Thornton
Keyword(s):  
Ligand Similarity ◽  
Biological Substrates

The High Resolution Appearance of Biological Substrates

1969 ◽  
Vol 27 ◽  
pp. 416-417
Author(s):  
Glen B. Haydon
Keyword(s):  
High Resolution ◽  
Phase Image ◽  
Biological Structure ◽  
Electron Microscopic ◽  
Thin Sections ◽  
Resolution Electron ◽  
Discrete Structures ◽  
Large Phase ◽  
Biological Substrates ◽  
High Resolution Electron Micrographs

High resolution electron microscopic study of negatively stained macromolecules and thin sections of tissue embedded in a variety of media are difficult to interpret because of the superimposed phase image granularity. Although all of the information concerning the biological structure of interest may be present in a defocused electron micrograph, the high contrast of large phase image granules produced by the substrate makes it impossible to distinguish the phase ‘points’ from discrete structures of the same dimensions. Theory predicts the findings; however, it does not allow an appreciation of the actual appearance of the image under various conditions. Therefore, though perhaps trivial, training of the cheapest computer produced by mass labor has been undertaken in order to learn to appreciate the factors which affect the appearance of the background in high resolution electron micrographs.

D3R Grand Challenge 4: Ligand Similarity and MM-GBSA-Based Pose Prediction and Affinity Ranking for BACE-1 Inhibitors

2019 ◽  
Author(s):  
Sukanya Sasmal ◽  
Léa El Khoury ◽  
David Mobley
Keyword(s):  
Binding Mode ◽  
Energy Estimates ◽  
Poor Correlation ◽  
Grand Challenge ◽  
Pose Prediction ◽  
Design Data ◽  
Data Resource ◽  
Affinity Ranking ◽  
Ligand Similarity ◽  
Bace 1

The Drug Design Data Resource (D3R) Grand Challenges present an opportunity to assess, in the context of a blind predictive challenge, the accuracy and the limits of tools and methodologies designed to help guide pharmaceutical drug discovery projects. Here, we report the results of our participation in the D3R Grand Challenge 4, which focused on predicting the binding poses and affinity ranking for compounds targeting the beta-amyloid precursor protein (BACE-1). Our ligand similarity-based protocol using HYBRID (OpenEye Scientific Software) successfully identified poses close to the native binding mode for most of the ligands with less than 2 A RMSD accuracy. Furthermore, we compared the performance of our HYBRID-based approach to that of AutoDock Vina and Dock 6 and found that HYBRID performed better here for pose prediction. We also conducted end-point free energy estimates on protein-ligand complexes using molecular mechanics combined with generalized Born surface area method (MM-GBSA). We found that the binding affinity ranking based on MM-GBSA scores have poor correlation with the experimental values. Finally, the main lessons from our participation in D3R Grand Challenge 4 suggest that: i) the generation of the macrocycles conformers is a key step for successful pose prediction, ii) the protonation states of the BACE-1 binding site should be treated carefully, iii) the MM-GBSA method could not discriminate well between different predicted binding poses, and iv) the MM-GBSA method does not perform well at predicting protein-ligand binding affinities here.

Biological substrates for metal preconcentration and speciation

1997 ◽  
Vol 16 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Yolanda Madrid ◽  
Carmen Cámara
Keyword(s):  
Biological Substrates

scholarly journals Application of 3D Zernike descriptors to shape-based ligand similarity searching

2009 ◽  
Vol 1 (1) ◽  
Author(s):  
Vishwesh Venkatraman ◽  
Padmasini Ramji Chakravarthy ◽  
Daisuke Kihara
Keyword(s):  
Similarity Searching ◽  
Ligand Similarity

Theoretical and practical aspects in determining the current geochemical status of the Crimean peninsula and anthropogenic risk to public health

2021 ◽  
Author(s):  
Elena Evstafeva ◽  
Svetlana Tymchenko ◽  
Anna Bogdanova ◽  
Olga Zalata ◽  
Yuliia Boyarinceva ◽  
...  
Keyword(s):  
Human Body ◽  
Negative Impact ◽  
Chemical Elements ◽  
Ecological Monitoring ◽  
Crimean Peninsula ◽  
Mercury Analysis ◽  
Geographical Regions ◽  
Wide Range ◽  
Biological Substrates ◽  
Cadmium Selenium

<p>The implementation of basic principles of medical and ecological monitoring programs in Crimea previously reported in EGU proceedings consists of determining the content of a wide range of toxic, essential and rare earth elements in various biological substrates: soil, plants, water, human body. Biosubstrates are sampled in different locations with contrast natural and anthropogenic conditions: urbanized-rural, industrial-agricultural, natural resources. Lichens and poplar leaves are used as indicators of environmental contamination, particularly atmospheric pollution; liquid precipitation is used as an indicator showing the negative impact of air pollution on ecosystems; hair is used as an indicator of the total body intake of chemical elements. The update of databases, on some of the territories (Simferopol, Sevastopol, geographical regions with different soil characteristics, etc.) with regard to some of the elements (mercury, lead, cadmium, selenium, etc.) at this stage allowed to determine their biogeochemical status in conditions of intensive growth of anthropogenic load in recent years, and to compare it with the elemental status of the humans living in this territory. The databases for other types of territories continue to be extended, the relationship between morbidity to estimate of the environmental burden of disease for environmentally determined diseases (neurodegenerative, endocrine, respiratory, etc.) and chemical load on the territories, based on USEtox model; the functional state of target systems (nervous, immune, cardiovascular) and level of chemical elements in the human body and the overall elemental imbalance, is established. This has provided us with a degree of understanding on how the degree of population and individual health risk could be determined.</p><p>Mercury analysis was funded by RFBR according to the research project № 18-29-24212\19 entitled “Development of neutralization of mercury-containing waste without heating and the formation of wastewater”, 2018–2021 years; elemental composition was possible to determine due to RFBR project № 18-45-920042\20 entitled “Bioecological monitoring of heavy metals at board of Black Sea of Crimea”, 2018–2020 years. Physiological part of research was possible to accomplish due to funds by the V.I. Vernadsky Crimean Federal University (Project No VG2019/15, АААА-А20-120012090158-7).</p>

Descriptive and illustrated diagnosis of Ophiuroidea fauna (Echinodermata) in the shallow waters of North-eastern Brazil

2015 ◽  
Vol 8 ◽  
Author(s):  
Fabilene Gomes Paim ◽  
Maria Cecília Guerrazzi ◽  
Michela Borges
Keyword(s):  
Brittle Star ◽  
Shallow Waters ◽  
Bottom Substrate ◽  
Eastern Brazil ◽  
North Eastern ◽  
Amphipholis Squamata ◽  
Biological Substrates ◽  
Almost All ◽  
First Time ◽  
Ophiocoma Echinata

In this study, we present descriptions, illustrations, comments, and bathymetric and geographic distributions of the brittle star species related to the estuary region of Camamu Bay, located in the State of Bahia, Brazil. The brittle star fauna lives on biological substrates, sand bottoms, mud and rubble in the Camamu Bay and comprises 12 species divided into five families. Almost all of them are common in the tropical and subtropical fauna of the regions of shallow water.Ophiophragmus filograneusis reported for the first time in Bahia, and nine other species are recorded for the first time in Camamu Bay:Amphipholis januarii, Amphipholis squamata, Ophiophragmus filograneus, Ophiostigma isocanthum,Ophioderma cinerea, Ophioderma januarii, Ophiactis lymani, Ophiactis savignyi andOphiocoma echinata.The results suggest that the ophiuroid assemblages are strongly affected by marine currents as well as by different kinds of bottom substrate.

scholarly journals The photochemical reactivity of triplet β-lapachone-3-sulfonic acid towards biological substrates

2010 ◽  
Vol 21 (6) ◽  
pp. 966-972 ◽  
Author(s):  
José C. Netto-Ferreira ◽  
Virginie Lhiaubet-Vallet ◽  
Andrea R. da Silva ◽  
Ari M. da Silva ◽  
Aurelio B. B. Ferreira ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Photochemical Reactivity ◽  
Biological Substrates

scholarly journals Autofluorescence spectroscopy and imaging: a tool for biomedical research and diagnosis

2014 ◽  
Author(s):  
A.C. Croce ◽  
G. Bottiroli
Keyword(s):  
Scientific Community ◽  
Data Interpretation ◽  
Near Ir ◽  
Endogenous Fluorophores ◽  
Biological Substrate ◽  
Autofluorescence Spectroscopy ◽  
Uv Visible ◽  
Biological Substrates ◽  
Relationship Of

Native fluorescence, or autofluorescence (AF), consists in the emission of light in the UV-visible, near-IR spectral range when biological substrates are excited with light at suitable wavelength. This is a well-known phenomenon, and the strict relationship of many endogenous fluorophores with morphofunctional properties of the living systems, influencing their AF emission features, offers an extremely powerful resource for directly monitoring the biological substrate condition. Starting from the last century, the technological progresses in microscopy and spectrofluorometry were convoying attention of the scientific community to this phenomenon. In the future, the interest in the autofluorescence will certainly continue. Current instrumentation and analytical procedures will likely be overcome by the unceasing progress in new devices for AF detection and data interpretation, while a progress is expected in the search and characterization of endogenous fluorophores and their roles as intrinsic biomarkers.

Beyond the facts in schizophrenia: closing the gaps in diagnosis, pathophysiology, and treatment

2011 ◽  
Vol 20 (4) ◽  
pp. 317-327 ◽  
Author(s):  
H. Nasrallah ◽  
R. Tandon ◽  
M. Keshavan
Keyword(s):  
Clinical Manifestations ◽  
Antipsychotic Treatment ◽  
Past Century ◽  
Disease Entity ◽  
Closing The Gaps ◽  
Distinct Disease ◽  
Extreme Variability ◽  
Biological Substrates ◽  
Single Disease Entity

Background.Although schizophrenia has been considered a distinct disease entity for the past century, its precise definition and etio-pathophysiology remain obscure and its treatment remains unsatisfactory. In this review, we summarize our state of knowledge about the etiology, pathophysiology, clinical features, and treatment of schizophrenia.Methodological Issues.The inadequacy of the major conceptual models of schizophrenia is a major roadblock in providing a coherent explanation for the known facts of this illness, despite these limitations and its changing definitions, the construct of schizophrenia does convey useful information: (i) patients diagnosed as having schizophrenia do have areal disease– they experience both suffering and disability; (ii) a diagnosis of schizophrenia does suggest adistinctive clinical profile– a characteristic long-term course; an admixture of positive, negative, and cognitive symptoms; (iii) a diagnosis of schizophrenia has clear treatment and prognostic implications – likelihood of benefit from antipsychotic treatment and likelihood of incomplete recovery; and (iv) schizophrenia satisfies criteria for a valid diagnostic entity better than almost any other psychiatric diagnosis.Discussion.On the other hand, the concept of schizophrenia has serious shortcomings. First, it is not a single disease entity – it has multiple etiological factors and pathophysiological mechanisms but common phenotypic features. Second, its clinical manifestations are so diverse that its extreme variability has been considered by some to be a core feature. Third, its boundaries remain ill defined and not clearly demarcated from other clinical entities.Conclusions.A necessary next step is to deconstruct schizophrenia as an entity into component dimensions –endophenotypes linked to unique etiological and pathophysiological processes that may yield unique treatment targets. Innovative approaches are needed to elucidate the biological substrates of these entities because such clarity is vital for replicable research. We conclude by identifying the critical gaps in our knowledge, and unmet needs in our approaches to care, and outline steps that can move the field forward.

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