Studies on Molecular Interactions between Bovine β-Lactoglobulin and Silver Nanoparticles

2020 ◽  
Vol 27 (8) ◽  
pp. 793-800
Author(s):  
Anchal Sharma ◽  
Kalyan Sundar Ghosh
Keyword(s):  
Silver Nanoparticles ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Cd Spectroscopy ◽  
Van Der Waals Interactions ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Different Temperatures ◽  
Β Lactoglobulin ◽  
Secondary And Tertiary Structure

Background: Silver Nanoparticles (AgNPs) were found to modulate the fibrillation of Bovine Β-Lactoglobulin (BLG). Objective: To gain an insight regarding the mechanism of BLG aggregation modulation by AgNPs at molecular level, studies on the interactions between BLG and AgNPs were carried out. Methods: Protein-ligand interactions were studied based on Trp fluorescence quenching (at four different temperatures), synchronous and three-dimensional fluorescence and circular dichroism spectroscopy (far-UV and near-UV). Results: Protein-nanoparticles association constant was in the range of 106 -1010 M-1 and the quenching constant was determined as ~107 M-1. Ground state complexation between the protein and nanoparticles was predicted. Change in polarity surrounding the Trp residue was not detected by synchronous and three-dimensional fluorescence spectroscopy. AgNPs caused a global change in the secondary and tertiary structure of the protein as revealed from far-UV and near-UV CD spectroscopy. Enthalpy driven complexation between the protein and nanoparticles indicates the involvement of hydrogen bonding and/or van der Waals interactions. Conclusion: Modulation of BLG aggregation by AgNPs is due to strong binding of the nanoparticles with BLG, which also causes structural perturbations of the protein.

Subunit δ of Chloroplast F0F1 ATPase and OSCP of Mitochondrial F0F1 ATPase: a Comparison by CD-Spectroscopy

1991 ◽  
Vol 46 (9-10) ◽  
pp. 759-764 ◽  
Author(s):  
Siegfried Engelbrecht ◽  
Jennifer Reed ◽  
François Penin ◽  
Danièle C. Gautheron ◽  
Wolfgang Junge
Keyword(s):  
Primary Structure ◽  
Tertiary Structure ◽  
Atp Synthesis ◽  
Structural Similarity ◽  
Cd Spectroscopy ◽  
Α Helix ◽  
And Function ◽  
High Degree ◽  
Very High ◽  
Secondary And Tertiary Structure

Abstract CD spectra have been recorded with subunit δ from chloroplast CF0CF1 and with OSCP from mitochondrial MF0MF1. These subunits are supposed to act similarly at the interface between proton transport through the F0-portion and ATP-synthesis in the F1-portion of their respective F0F1-ATPase. Evaluation of the data for both proteins revealed a very high α-helix content of -85% and practically no β-sheets. Despite their low homology on the primary structure level (23% identity) and their different electrostatic properties (pl-values differ by 3 units), spinach δ and porcine OSCP are indistinguishable with respect to their secondary structure as measured by CD. Prediction and analysis of consensual a-helices even in poorly conserved regions indicate α high degree of structural similarity between chloroplast δ and OSCP. In view of the topology and function of δ and OSCP in intact F0F1 these findings are interpreted to indicate the dominance of secondary and tertiary structure over the primary structure in their supposed function between proton flow and ATP-synthesis.

scholarly journals Preorganization in biological systems: Are conformational constraints worth the energy?

2007 ◽  
Vol 79 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Stephen F. Martin
Keyword(s):  
Experimental Evidence ◽  
Binding Affinity ◽  
Three Dimensional ◽  
Common Belief ◽  
Flexible Control ◽  
Protein Ligand Interactions ◽  
Conformational Constraints ◽  
Ligand Interactions ◽  
Dimensional Shape ◽  
Three Dimensional Shape

It is generally assumed that preorganizing a flexible ligand in the three-dimensional shape it adopts when bound to a macromolecular receptor will provide a derivative having an increased binding affinity, primarily because the rigidified molecule is expected to benefit from a lesser entropic penalty during complexation. We now provide the first experimental evidence that demonstrates this common belief is not universally true. Indeed, we find that ligand preorganization may be accompanied by an unfavorable entropy of binding, even when the constrained ligand exhibits a higher binding affinity than its flexible control. Thus, the effects that ligand preorganization have upon energetics and structure in protein-ligand interactions must be reevaluated.

scholarly journals High-resolution cryo-EM proteasome structures in drug development

2017 ◽  
Vol 73 (6) ◽  
pp. 522-533 ◽  
Author(s):  
Edward P. Morris ◽  
Paula C. A. da Fonseca
Keyword(s):  
Structure Determination ◽  
Protein Structures ◽  
Three Dimensional ◽  
Specific Inhibitor ◽  
Particle Analysis ◽  
20S Proteasome ◽  
Ligand Specificity ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Dimensional Reconstruction

With the recent advances in biological structural electron microscopy (EM), protein structures can now be obtained by cryo-EM and single-particle analysis at resolutions that used to be achievable only by crystallographic or NMR methods. We have explored their application to study protein–ligand interactions using the human 20S proteasome, a well established target for cancer therapy that is also being investigated as a target for an increasing range of other medical conditions. The map of a ligand-bound human 20S proteasome served as a proof of principle that cryo-EM is emerging as a realistic approach for more general structural studies of protein–ligand interactions, with the potential benefits of extending such studies to complexes that are unfavourable to other methods and allowing structure determination under conditions that are closer to physiological, preserving ligand specificity towards closely related binding sites. Subsequently, the cryo-EM structure of thePlasmodium falciparum20S proteasome, with a new prototype specific inhibitor bound, revealed the molecular basis for the ligand specificity towards the parasite complex, which provides a framework to guide the development of highly needed new-generation antimalarials. Here, the cryo-EM analysis of the ligand-bound human andP. falciparum20S proteasomes is reviewed, and a complete description of the methods used for structure determination is provided, including the strategy to overcome the bias orientation of the human 20S proteasome on electron-microscope grids and details of theicr3dsoftware used for three-dimensional reconstruction.

scholarly journals IntFOLD: an integrated web resource for high performance protein structure and function prediction

2019 ◽  
Vol 47 (W1) ◽  
pp. W408-W413 ◽  
Author(s):  
Liam J McGuffin ◽  
Recep Adiyaman ◽  
Ali H A Maghrabi ◽  
Ahmad N Shuid ◽  
Danielle A Brackenridge ◽  
...  
Keyword(s):  
High Performance ◽  
Tertiary Structure ◽  
Structural Domain ◽  
Model Quality ◽  
Tertiary Structures ◽  
Performance Improvements ◽  
Web Resource ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
And Function

Abstract The IntFOLD server provides a unified resource for the automated prediction of: protein tertiary structures with built-in estimates of model accuracy (EMA), protein structural domain boundaries, natively unstructured or disordered regions in proteins, and protein–ligand interactions. The component methods have been independently evaluated via the successive blind CASP experiments and the continual CAMEO benchmarking project. The IntFOLD server has established its ranking as one of the best performing publicly available servers, based on independent official evaluation metrics. Here, we describe significant updates to the server back end, where we have focused on performance improvements in tertiary structure predictions, in terms of global 3D model quality and accuracy self-estimates (ASE), which we achieve using our newly improved ModFOLD7_rank algorithm. We also report on various upgrades to the front end including: a streamlined submission process, enhanced visualization of models, new confidence scores for ranking, and links for accessing all annotated model data. Furthermore, we now include an option for users to submit selected models for further refinement via convenient push buttons. The IntFOLD server is freely available at: http://www.reading.ac.uk/bioinf/IntFOLD/.

scholarly journals Novel Protease Inhibitors (PIs) Containing Macrocyclic Components and 3(R),3a(S),6a(R)-bis-Tetrahydrofuranylurethane That Are Potent against Multi-PI-Resistant HIV-1 Variants In Vitro

2010 ◽  
Vol 54 (8) ◽  
pp. 3460-3470 ◽  
Author(s):  
Yasushi Tojo ◽  
Yasuhiro Koh ◽  
Masayuki Amano ◽  
Manabu Aoki ◽  
Debananda Das ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Molecular Design ◽  
Antiviral Agent ◽  
Structural Features ◽  
Biological Properties ◽  
Van Der Waals Interactions ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Hiv 1

ABSTRACT Natural products with macrocyclic structural features often display intriguing biological properties. Molecular design incorporating macrocycles may lead to molecules with unique protein-ligand interactions. We generated novel human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a macrocycle and bis-tetrahydrofuranylurethane. Four such compounds exerted potent activity against HIV-1LAI and had 50% effective concentrations (EC50s) of as low as 0.002 μM with minimal cytotoxicity. GRL-216 and GRL-286 blocked the replication of HIV-1NL4-3 variants selected by up to 5 μM saquinavir, ritonavir, nelfinavir, lopinavir, or atazanavir; they had EC50s of 0.020 to 0.046 μM and potent activities against six multi-PI-resistant clinical HIV-1 (HIVmPIr ) variants with EC50s of 0.027 to 0.089 μM. GRL-216 and -286 also blocked HIV-1 protease dimerization as efficiently as darunavir. When HIV-1NL4-3 was selected by GRL-216, it replicated progressively more poorly and failed to replicate in the presence of >0.26 μM GRL-216, suggesting that the emergence of GRL-216-resistant HIV-1 variants is substantially delayed. At passage 50 with GRL-216 (the HIV isolate selected with GRL-216 at up to 0.16 μM [HIV216-0.16 μM]), HIV-1NL4-3 containing the L10I, L24I, M46L, V82I, and I84V mutations remained relatively sensitive to PIs, including darunavir, with the EC50s being 3- to 8-fold-greater than the EC50 of each drug for HIV-1NL4-3. Interestingly, HIV216-0.16 μM had 10-fold increased sensitivity to tipranavir. Analysis of the protein-ligand X-ray structures of GRL-216 revealed that the macrocycle occupied a greater volume of the binding cavity of protease and formed greater van der Waals interactions with V82 and I84 than darunavir. The present data warrant the further development of GRL-216 as a potential antiviral agent for treating individuals harboring wild-type and/or HIVmPIr .

scholarly journals Layer-wise relevance propagation of InteractionNet explains protein–ligand interactions at the atom level

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hyeoncheol Cho ◽  
Eok Kyun Lee ◽  
Insung S. Choi
Keyword(s):  
Dissociation Constants ◽  
Structural Information ◽  
Three Dimensional ◽  
Graph Representation ◽  
Ligand Complex ◽  
Covalent Bonds ◽  
Protein Ligand Interactions ◽  
Ligand Interactions ◽  
Atom Level ◽  
Graph Neural Networks

AbstractDevelopment of deep-learning models for intermolecular noncovalent (NC) interactions between proteins and ligands has great potential in the chemical and pharmaceutical tasks, including structure–activity relationship and drug design. It still remains an open question how to convert the three-dimensional, structural information of a protein–ligand complex into a graph representation in the graph neural networks (GNNs). It is also difficult to know whether a trained GNN model learns the NC interactions properly. Herein, we propose a GNN architecture that learns two distinct graphs—one for the intramolecular covalent bonds in a protein and a ligand, and the other for the intermolecular NC interactions between the protein and the ligand—separately by the corresponding covalent and NC convolutional layers. The graph separation has some advantages, such as independent evaluation on the contribution of each convolutional step to the prediction of dissociation constants, and facile analysis of graph-building strategies for the NC interactions. In addition to its prediction performance that is comparable to that of a state-of-the art model, the analysis with an explainability strategy of layer-wise relevance propagation shows that our model successfully predicts the important characteristics of the NC interactions, especially in the aspect of hydrogen bonding, in the chemical interpretation of protein–ligand binding.

scholarly journals Docking studies in targeting proteins involved in cardiovascular disorders using phytocompounds from Terminalia arjuna

2020 ◽  
Author(s):  
Vikas Kumar ◽  
Nitin Sharma ◽  
Anuradha Sourirajan ◽  
Prem Kumar Khosla ◽  
Kamal Dev
Keyword(s):  
Molecular Docking ◽  
3D Structure ◽  
Three Dimensional ◽  
Data Bank ◽  
Docking Studies ◽  
Terminalia Arjuna ◽  
Structure Based Drug Design ◽  
Lipinski’S Rule ◽  
Protein Ligand Interactions ◽  
Ligand Interactions

AbstractTerminalia arjuna (Roxb.) Wight and Arnot (T. arjuna) commonly known as Arjuna has been known for its cardiotonic nature in heart failure, ischemic, cardiomyopathy, atherosclerosis, myocardium necrosis and also has been used in the treatment of different human disorders such as blood diseases, anaemia and viral diseases. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant cardioprotective activity. Since Protein-Ligand interactions play a key role in structure-based drug design, therefore with the help of molecular docking, we screened 19 phytochemicals present in T. arjuna and investigated their binding affinity against different cardiovascular target proteins. The three-dimensional (3D) structure of target cardiovascular proteins were retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 19 phytochemicals using Autodock vina. Molecular docking and drug-likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their cardio protective activity. Among all selected phytocompounds, arjunic acid, arjungenin, and terminic acid were found to fulfill all ADMET rules, drug likeness, and are less toxic in nature. Our studies, therefore revealed that these three phytochemicals from T. arjuna can be used as promising candidates for developing broad spectrum drugs against cardiovascular diseases.

Understanding EHDA and Protein Stability

2007 ◽  
Author(s):  
Elizabeth M. Nottingham ◽  
Michelle G. Zeles-Hahn ◽  
Corinne S. Lengsfeld
Keyword(s):  
Electrostatic Interactions ◽  
Tertiary Structure ◽  
Therapeutic Proteins ◽  
Three Dimensional ◽  
The Body ◽  
Hydrophilic Interactions ◽  
Dimensional Shape ◽  
Physical Forces ◽  
Three Dimensional Shape ◽  
Secondary And Tertiary Structure

Therapeutic proteins can be difficult to work with due to the fact that each protein has properties and functions that are unique. These exclusive properties are in part due to the proteins three-dimensional shape (secondary and tertiary structure). This shape is determined by bends in the amino acid sequence generated by electrostatic interactions, hydrogen bonds, and hydrophobic-hydrophilic interactions between neighboring amino acids. These bonding interactions are weak and can be severed by chemical or physical forces. Thus, therapeutic proteins can be denatured during manufacture and by methods used to deliver them to the body.

Studies of protein–ligand interactions by NMR

2003 ◽  
Vol 31 (5) ◽  
pp. 1006-1009 ◽  
Author(s):  
J. Clarkson ◽  
I.D. Campbell
Keyword(s):  
Chemical Shift ◽  
Structure Determination ◽  
Dissociation Constants ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Ligand Complex ◽  
Protein Ligand Interactions ◽  
Small Proteins ◽  
Ligand Interactions

Solution-state NMR has become an accepted method for studying the structure of small proteins in solution. This has resulted in over 3000 NMR-based co-ordinate sets being deposited in the Protein Databank. It is becoming increasingly apparent, however, that NMR is also a very powerful tool for accessing interactions between macromolecules and various ligands. These interactions can be assessed at a wide variety of levels, e.g. qualitative screening of libraries of pharmaceuticals and ‘chemical shift mapping’. Dissociation constants can sometimes be obtained in such cases. Another example would be the complete three-dimensional structure determination of a protein–ligand complex. Here we briefly describe a few of the principles involved and illustrate the method with recent examples.

Calorimetric and Spectroscopic investigations οf β-lactoglobulin upon interaction with copper ion

2012 ◽  
Vol 79 (2) ◽  
pp. 209-215 ◽  
Author(s):  
Adeleh Divsalar ◽  
Sajedeh Ebrahim Damavandi ◽  
Ali Akbar Saboury ◽  
Arefeh Seyedarabi ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Tertiary Structure ◽  
Copper Ions ◽  
Copper Ion ◽  
Industrial Applications ◽  
Titration Calorimetry ◽  
Different Temperatures ◽  
Uv Visible ◽  
Cd Studies ◽  
Effect Of Copper ◽  
Β Lactoglobulin

The effect of copper(II) ions (Cu+2) on the structure of β-lactoglobulin (β-lg) was investigated spectroscopically using UV-visible, fluorescence and circular dichroism (CD) and calorimetrically using isothermal titration calorimetry (ITC), at different temperatures. Results of the UV-visible studies showed that adding Cu+2 to β-lg solution caused increasing turbidity, indicative of protein aggregation. It was noticeable that the rate of increasing turbidity was directly proportional to increasing temperature. The far-UV CD studies displayed that the Cu+2 cannot induce any significant changes in the secondary structures of β-lg at different temperatures. Also, the ITC data indicated that the binding process of Cu+2 to β-lg is mainly entropically driven. The results highlight that copper ions cause the tertiary structure of β-lg to change and induce a slightly open structure leading to the formation of supramolecular aggregates in β-lg which may result in the reduced allergenicity of β-lg and its increased use in industrial applications.

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