scholarly journals Moving pictures: Reassessing docking experiments with a dynamic view of protein interfaces

2020 ◽  
Author(s):  
Chantal Prévost ◽  
Sophie Sacquin-Mora
Keyword(s):  
Protein Interactions ◽  
Protein Interface ◽  
Protein Interfaces ◽  
Reference Protein ◽  
Dynamic Perspective ◽  
Set Up ◽  
The Stability ◽  
Dynamics Simulations ◽  
Dynamic Quality

The modeling of protein assemblies on the atomic level remains a central issue in structural biology, as protein interactions play a key role in numerous cellular processes. This problem is traditionally addressed using docking tools, where the quality of the models that are produced is based on their similarity to a single reference experimental structure. However, this approach using a static reference does not take into account the dynamic quality of the protein interface. Here, we used all-atom classical Molecular Dynamics simulations to investigate the stability of the interface for three complexes that previously served as targets in the CAPRI competition, and for each one of these targets, ten models distributed over the High, Medium and Acceptable categories. To assess the quality of these models from a dynamic perspective, we set up new criteria which take into account the stability of the reference protein interface. We show that, when the protein interfaces are allowed to evolve along time, the original ranking based on the static CAPRI criteria no longer holds as over 50% of the docking models undergo a category change (either toward a better or a lower group) when reassessing their quality using dynamic information.

scholarly journals Set-up and screening of a fragment library targeting the 14-3-3 protein interface

MedChemComm ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 1796-1802 ◽  
Author(s):  
Dario Valenti ◽  
João Filipe Neves ◽  
François-Xavier Cantrelle ◽  
Stanimira Hristeva ◽  
Domenico Lentini Santo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Protein Interactions ◽  
Low Molecular Weight ◽  
Protein Interface ◽  
Protein Protein Interactions ◽  
Fragment Library ◽  
Set Up

Fragment-based driven discovery of 3 new low molecular weight starting points for the modulation of 14-3-3 protein–protein interactions.

Effect of Structural Variability of the Ceramide Part on the Saccharide-Ceramide Linkage in Model Glycolipids Studied by Molecular Mechanics and Molecular Dynamics Methods

1996 ◽  
Vol 61 (10) ◽  
pp. 1405-1431
Author(s):  
Zuzana Gálová ◽  
Tibor Kožár
Keyword(s):  
Molecular Dynamics ◽  
Molecular Mechanics ◽  
Energy Surface ◽  
Structural Parameters ◽  
Structural Variability ◽  
Molecular Dynamics Methods ◽  
Set Up ◽  
The Stability ◽  
Dynamics Simulations ◽  
Torsional Angles

Conformational analysis was performed for model glycosphingolipid molecules with a view to studying the effect of structural variability of the lipidic part and its flexibility on the saccharide-ceramide linkage. In addition to systematic and random molecular mechanics sampling techniques (the RAMM program), molecular dynamics simulations (Biosym DISCOVER program) were carried out to analyze the conformational energy surface of the model glycolipid molecules. The influence of the structural variability and flexibility of the lipidic part is demonstrated by prediction of the stability of different conformations around the carbohydrate-ceramide linkage. The α2, α1 and Θ1 torsional angles are the most important structural parameters with respect to the carbohydrate-ceramide connection. Two dominant conformations for the saccharide-ceramide linkage were observed, with the α2/α1/Θ1 dihedral angles in the -sc/+ac/ap and -sc/ap/-sc regions. While each of the calculation methods predicts similar flexibility in the α2/α1 space, the flexibility around the Θ1 angle differs considerably, reflecting the parametrization and set-up of the modelling protocol.

scholarly journals PPCheck: A Webserver for the Quantitative Analysis of Protein-Protein Interfaces and Prediction of Residue Hotspots

2015 ◽  
Vol 9 ◽  
pp. BBI.S25928 ◽  
Author(s):  
Anshul Sukhwal ◽  
Ramanathan Sowdhamini
Keyword(s):  
Protein Interactions ◽  
Test Cases ◽  
Protein Interface ◽  
Protein Protein Interactions ◽  
Alanine Scanning ◽  
Conserved Residues ◽  
Protein Interfaces ◽  
Computational Alanine Scanning ◽  
Key Residues ◽  
Better Than

Background Modeling protein-protein interactions (PPIs) using docking algorithms is useful for understanding biomolecular interactions and mechanisms. Typically, a docking algorithm generates a large number of docking poses, and it is often challenging to select the best native-like pose. A further challenge is to recognize key residues, termed as hotspots, at protein-protein interfaces, which contribute more in stabilizing a protein-protein interface. Results We had earlier developed a computer algorithm, called PPCheck, which ascribes pseudoenergies to measure the strength of PPIs. Native-like poses could be successfully identified in 27 out of 30 test cases, when applied on a separate set of decoys that were generated using FRODOCK. PPCheck, along with conservation and accessibility scores, was able to differentiate ‘native-like and non-native-like poses from 1883 decoys of Critical Assessment of Prediction of Interactions (CAPRI) targets with an accuracy of 60%. PPCheck was trained on a 10-fold mixed dataset and tested on a 10-fold mixed test set for hotspot prediction. We obtain an accuracy of 72%, which is in par with other methods, and a sensitivity of 59%, which is better than most existing methods available for hotspot prediction that uses similar datasets. Other relevant tests suggest that PPCheck can also be reliably used to identify conserved residues in a protein and to perform computational alanine scanning. Conclusions PPCheck webserver can be successfully used to differentiate native-like and non-native-like docking poses, as generated by docking algorithms. The webserver can also be a convenient platform for calculating residue conservation, for performing computational alanine scanning, and for predicting protein-protein interface hotspots. While PPCheck can differentiate the generated decoys into native-like and non-native-like decoys with a fairly good accuracy, the results improve dramatically when features like conservation and accessibility are included. The method can be successfully used in ranking/scoring the decoys, as obtained from docking algorithms.

PPiClust: EFFICIENT CLUSTERING OF 3D PROTEIN–PROTEIN INTERACTION INTERFACES

2008 ◽  
Vol 06 (03) ◽  
pp. 415-433 ◽  
Author(s):  
ZEYAR AUNG ◽  
SOON-HENG TAN ◽  
SEE-KIONG NG ◽  
KIAN-LEE TAN
Keyword(s):  
Protein Interactions ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Structural Data ◽  
Structural Basis ◽  
Protein Interface ◽  
Clustering Methods ◽  
Protein Protein Interaction ◽  
Protein Interfaces ◽  
Complex Structural

The biological mechanisms through which proteins interact with one another are best revealed by studying the structural interfaces between interacting proteins. Protein–protein interfaces can be extracted from three-dimensional (3D) structural data of protein complexes and then clustered to derive biological insights. However, conventional protein interface clustering methods lack computational scalability and statistical support. In this work, we present a new method named "PPiClust" to systematically encode, cluster, and analyze similar 3D interface patterns in protein complexes efficiently. Experimental results showed that our method is effective in discovering visually consistent and statistically significant clusters of interfaces, and at the same time sufficiently time-efficient to be performed on a single computer. The interface clusters are also useful for uncovering the structural basis of protein interactions. Analysis of the resulting interface clusters revealed groups of structurally diverse proteins having similar interface patterns. We also found, in some of the interface clusters, the presence of well-known linear binding motifs which were noncontiguous in the primary sequences. These results suggest that PPiClust can discover not only statistically significant, but also biologically significant, protein interface clusters from protein complex structural data.

Criteria for evaluation of the coordinate measurements quality of parts geometric parameters at pilot-experimental production

2019 ◽  
pp. 3-8
Author(s):  
N.Yu. Bobrovskaya ◽  
M.F. Danilov
Keyword(s):  
Quality Indicators ◽  
Quality Management System ◽  
Technical Specification ◽  
Experimental Production ◽  
Technological Heredity ◽  
Coordinate Measurements ◽  
Reasonable Choice ◽  
The Stability ◽  
Geometric Elements

The criteria of the coordinate measurements quality at pilot-experimental production based on contemporary methods of quality management system and traditional methods of the measurements quality in Metrology are considered. As an additional criterion for quality of measurements, their duration is proposed. Analyzing the problem of assessing the quality of measurements, the authors pay particular attention to the role of technological heredity in the analysis of the sources of uncertainty of coordinate measurements, including not only the process of manufacturing the part, but all stages of the development of design and technological documentation. Along with such criteria as the degree of confidence in the results of measurements; the accuracy, convergence, reproducibility and speed of the results must take into account the correctness of technical specification, and such characteristics of the shape of the geometric elements to be controlled, such as flatness, roundness, cylindrical. It is noted that one of the main methods to reduce the uncertainty of coordinate measurements is to reduce the uncertainty in the initial data and measurement conditions, as well as to increase the stability of the tasks due to the reasonable choice of the basic geometric elements (measuring bases) of the part. A prerequisite for obtaining reliable quality indicators is a quantitative assessment of the conditions and organization of the measurement process. To plan and normalize the time of measurements, the authors propose to use analytical formulas, on the basis of which it is possible to perform quantitative analysis and optimization of quality indicators, including the speed of measurements.

The Role of Hydrophobicity in the Stability and pH-Switchability of (RXDX)4 and Coumarin-RXDX Conjugate β-Sheets

2020 ◽  
Author(s):  
Ryan Weber ◽  
Martin McCullagh
Keyword(s):  
Biological Imaging ◽  
Ph Sensing ◽  
Hydrophobic Residue ◽  
Ideal Candidate ◽  
Self Assembling ◽  
Sensing Applications ◽  
Β Sheets ◽  
The Stability ◽  
Dynamics Simulations

<p>pH-switchable, self-assembling materials are of interest in biological imaging and sensing applications. Here we propose that combining the pH-switchability of RXDX (X=Ala, Val, Leu, Ile, Phe) peptides and the optical properties of coumarin creates an ideal candidate for these materials. This suggestion is tested with a thorough set of all-atom molecular dynamics simulations. We first investigate the dependence of pH-switchabiliy on the identity of the hydrophobic residue, X, in the bare (RXDX)<sub>4</sub> systems. Increasing the hydrophobicity stabilizes the fiber which, in turn, reduces the pH-switchabilty of the system. This behavior is found to be somewhat transferable to systems in which a single hydrophobic residue is replaced with a coumarin containing amino acid. In this case, conjugates with X=Ala are found to be unstable and both pHs while conjugates with X=Val, Leu, Ile and Phe are found to form stable β-sheets at least at neutral pH. The (RFDF)<sub>4</sub>-coumarin conjugate is found to have the largest relative entropy value of 0.884 +/- 0.001 between neutral and acidic coumarin ordering distributions. Thus, we posit that coumarin-(RFDF)<sub>4</sub> containing peptide sequences are ideal candidates for pH-sensing bioelectronic materials.</p>

Statistical Management of Food Production Processes

2020 ◽  
pp. 30-35
Author(s):  
N.A. Jurk ◽  
Keyword(s):  
Production Process ◽  
Control Chart ◽  
Food Production ◽  
Time Interval ◽  
Bakery Products ◽  
Shewhart Control ◽  
Manufactured Products ◽  
Mnemonic Technique ◽  
The Stability

The article presents scientific research in the field of statistical controllability of the food production process using the example of bakery products for a certain time interval using statistical methods of quality management. During quality control of finished products, defects in bakery products were identified, while the initial data were recorded in the developed form of a checklist for registering defects. It has been established that the most common defect is packaging leakage. For the subsequent statistical assessment of the stability of the production process and further analysis of the causes of the identified defect, a Shewhart control chart (p-card by an alternative feature) was used, which allows you to control the quality of manufactured products by the number of defects detected. Analyzing the control chart, it was concluded that studied process is conditionally stable, and the emerging defects are random. At the last stage of the research, the Ishikawa causal diagram was used, developed using the 6M mnemonic technique, in order to identify the most significant causes that affect the occurrence of the considered defect in bakery products. A more detailed study will allow the enterprise to produce food products that meet the established requirements.

STUDY OF INACCURACY IN THE OPERATION OF THE MAIN CONTROLLER OF STB MACHINE

2019 ◽  
Keyword(s):  
Normal Distribution ◽  
Stable Process ◽  
Random Errors ◽  
Actual Length ◽  
Experimental Data Processing ◽  
Set Up ◽  
Main Regulator ◽  
Transmission Gear ◽  
Selection Of

At production of fabrics, including fabrics for agricultural purpose, an important role is played by the cor-rect adjustment of operation of machine main regulator. The quality of setup of machine main controller is determined by the proper selection of rotation angle of warp beam weaving per one filling thread. In the pro-cess of using the regulator as a result of mistakes in adjustment, wear of transmission gear and backlashes in connections of details there are random changes in threads length. The purpose of the article is the research of property of random errors of basis giving by STB machine regulator. Mistakes can be both negative, and positive. In case of emergence only negative or only positive mistakes operation of the machine becomes im-possible as there will be a consecutive accumulation of mistakes. As a result of experimental data processing for stable process of weaving and the invariable diameter of basis threads winding of threads it is revealed that the random error of giving is set up as linear function of the accidental length having normal distribution. Measurements of accidental deviations in giving of a basis by the main regulator allowed to construct a curve of normal distribution of its actual length for one pass of weft thread. The presented curve of distribution of random errors in giving of a basis is the displaced curve of normal distribution of the accidental sizes. Also we define the density of probability of normal distribution of basis giving errors connected with a margin er-ror operation of the main regulator knowing of which allows to plan ways of their decrease that is important for improvement of quality of the produced fabrics.

The Rotterdam Initiative in Reducing Waste Discharges at Source

1991 ◽  
Vol 24 (10) ◽  
pp. 171-177
Author(s):  
T. Vellinga ◽  
J. P. J. Nijssen
Keyword(s):  
Public Relations ◽  
Action Plan ◽  
Detailed Balance ◽  
River Rhine ◽  
The North ◽  
Complementary Role ◽  
Action Programme ◽  
The North Sea ◽  
Set Up

Much of the material dredged from the port of Rotterdam is contaminated to such a degree that it must be placed in specially constructed sites. The aim of Rotterdam is to ensure that the dredged material will once again be clean. This will entail the thorough cleansing of the sources of the contamination of the sediment in the harbours and in the River Rhine. The Rotterdam Rhine Research Project (RRP) is one of the means to achieve this based on: technical research, legal research, public relations and dialogues with dischargers. The programme for five selected heavy metals is almost complete. For many heavy metal discharge points between Rotterdam and Rheinfelden, a specially devised independent load assessment has been carried out four times. Balance studies were used to determine the relative contributions of the point discharges to the total. Currently the results are being used in an attempt to negotiate agreements with a selected number of the major dischargers. At present, more detailed balance studies are being set up and exploratory measurements carried out for organic micropollutants. It may be concluded that the research is progressing successfully and methods and techniques developed seem satisfactory and broadly applicable. The Rhine Action Programme encompasses an international effort to improve the quality of the Rhine water. Although the RRP plays a modest complementary role to the Rhine Action Plan, there is no doubt of the value of this Rotterdam initiative. The mode of work followed in the RRP contains elements that can be of use in combatting the contamination of the North Sea by rivers other than the Rhine.

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