scholarly journals CAVIAR: a method for automatic cavity detection, description and decomposition into subcavities

2021 ◽  
Author(s):  
Jean-Rémy Marchand ◽  
Bernard Pirard ◽  
Peter Ertl ◽  
Finton Sirockin
Keyword(s):  
Machine Learning ◽  
Binding Sites ◽  
Protein Structures ◽  
Cavity Detection ◽  
Protein Binding Sites ◽  
Machine Learning Methods ◽  
Software Code ◽  
Dynamics Simulations ◽  
Hit Identification

<p></p><p>The accurate description of protein binding sites is essential to the determination of similarity and the application of machine learning methods to relate the binding sites to observed functions. This work describes CAVIAR, a new open source tool for generating descriptors for binding sites, using protein structures in PDB and mmCIF format as well as trajectory frames from molecular dynamics simulations as input. The applicability of CAVIAR descriptors is showcased by computing machine learning predictions of binding site ligandability. The method can also automatically assign subcavities, even in the absence of a bound ligand. The defined subpockets mimic the empirical definitions used in medicinal chemistry projects. It is shown that the experimental binding affinity scales relatively well with the number of subcavities filled by the ligand, with compounds binding to more than three subcavities having nanomolar or better affinities to the target. The CAVIAR descriptors and methods can be used in any machine learning-based investigations of problems involving binding sites, from protein engineering to hit identification. The full software code is available on GitHub and a conda package is hosted on Anaconda cloud.</p><p></p>

scholarly journals An Isotopic Method for the Determination of Vitamin B12 Levels in Blood

Blood ◽  
1963 ◽  
Vol 21 (1) ◽  
pp. 70-79 ◽  
Author(s):  
RUSSEL M. BARAKAT ◽  
ROGER P. EKINS
Keyword(s):  
Vitamin B12 ◽  
Binding Sites ◽  
Specific Activity ◽  
Specific Binding ◽  
Normal Subjects ◽  
Free Form ◽  
Protein Binding Sites ◽  
Isotopic Method ◽  
Specific Binding Protein

Abstract Vitamin B12 is normally present in plasma mainly bound to a specific binding protein. Addition of exogenous vitamin ultimately results in saturation of protein binding sites and excess vitamin remains in free form. The ratio of free to bound fractions thus quantitatively depends upon the concentration of exogenous compound. This observation has been utilized to determine amounts of vitamin B12 extracted from the blood of normal subjects and of patients with certain pathologic conditions. The method is simple and reproducible. The sensitivity of the method is such that vitamin levels down to roughly 20 µµg./ml. may be evaluated using labeled vitamin B12 of a specific activity of about 1 µc./µg. Repeated assays on identical specimens of normal plasma have shown a reproducibility of about 5-6 per cent. Results on 39 normal subjects gave a range of 330-1070 µµg./ml. with an average of 611 ± 167. Values observed in plasma taken from patients suffering from pernicious anemia were around 100 µµg./ml. or less. Results on subjects with other pathologic conditions are also presented and the limitations of the method are discussed.

Searching for protein binding sites from Molecular Dynamics simulations and paramagnetic fragment-based NMR studies

2014 ◽  
Vol 1844 (3) ◽  
pp. 561-566 ◽  
Author(s):  
Andrea Bernini ◽  
Lucia Henrici De Angelis ◽  
Edoardo Morandi ◽  
Ottavia Spiga ◽  
Annalisa Santucci ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Binding ◽  
Molecular Dynamics Simulations ◽  
Binding Sites ◽  
Nmr Studies ◽  
Protein Binding Sites ◽  
Dynamics Simulations

A QUANTITATIVE ANALYSIS OF INTERFACIAL AMINO ACID CONSERVATION IN PROTEIN-PROTEIN HETERO COMPLEXES

2005 ◽  
Vol 03 (05) ◽  
pp. 1137-1150 ◽  
Author(s):  
BOOJALA V. B. REDDY ◽  
YIANNIS N. KAZNESSIS
Keyword(s):  
Amino Acid ◽  
Protein Binding ◽  
Binding Sites ◽  
Protein Structures ◽  
Complex Structures ◽  
Protein Surface ◽  
Protein Surfaces ◽  
Protein Binding Sites ◽  
Interaction Sites ◽  
Conserved Residue

A long-standing question in molecular biology is whether interfaces of protein-protein complexes are more conserved than the rest of the protein surfaces. Although it has been reported that conservation can be used as an indicator for predicting interaction sites on proteins, there are recent reports stating that the interface regions are only slightly more conserved than the rest of the protein surfaces, with conservation signals not being statistically significant enough for predicting protein-protein binding sites. In order to properly address these controversial reports we have studied a set of 28 well resolved hetero complex structures of proteins that consists of transient and non-transient complexes. The surface positions were classified into four conservation classes and the conservation index of the surface positions was quantitatively analyzed. The results indicate that the surface density of highly conserved positions is significantly higher in the protein-protein interface regions compared with the other regions of the protein surface. However, the average conservation index of the patches in the interface region is not significantly higher compared with other surface regions of the protein structures. This finding demonstrates that the number of conserved residue positions is a more appropriate indicator for predicting protein-protein binding sites than the average conservation index in the interacting region. We have further validated our findings on a set of 59 benchmark complex structures. Furthermore, an analysis of 19 complexes of antigen-antibody interactions shows that there is no conservation of amino acid positions in the interacting regions of these complexes, as expected, with the variable region of the immunoglobulins interacting mostly with the antigens. Interestingly, antigen interacting regions also have a higher number of non-conserved residue positions in the interacting region than the rest of the protein surface.

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