JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Intrinsically disordered proteins-relation to general model expressing the active role of the water environment.
Adv Protein Chem Struct Biol
PUBLISHED: 03-18-2014
Show Abstract
Hide Abstract
This work discusses the role of unstructured polypeptide chain fragments in shaping the protein's hydrophobic core. Based on the "fuzzy oil drop" model, which assumes an idealized distribution of hydrophobicity density described by the 3D Gaussian, we can determine which fragments make up the core and pinpoint residues whose location conflicts with theoretical predictions. We show that the structural influence of the water environment determines the positions of disordered fragments, leading to the formation of a hydrophobic core overlaid by a hydrophilic mantle. This phenomenon is further described by studying selected proteins which are known to be unstable and contain intrinsically disordered fragments. Their properties are established quantitatively, explaining the causative relation between the protein's structure and function and facilitating further comparative analyses of various structural models.
Related JoVE Video
The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function.
J. Theor. Biol.
PUBLISHED: 02-27-2014
Show Abstract
Hide Abstract
In this paper we show that the fuzzy oil drop model represents a general framework for describing the generation of hydrophobic cores in proteins and thus provides insight into the influence of the water environment upon protein structure and stability. The model has been successfully applied in the study of a wide range of proteins, however this paper focuses specifically on domains representing immunoglobulin-like folds. Here we provide evidence that immunoglobulin-like domains, despite being structurally similar, differ with respect to their participation in the generation of hydrophobic core. It is shown that ?-structural fragments in ?-barrels participate in hydrophobic core formation in a highly differentiated manner. Quantitatively measured participation in core formation helps explain the variable stability of proteins and is shown to be related to their biological properties. This also includes the known tendency of immunoglobulin domains to form amyloids, as shown using transthyretin to reveal the clear relation between amyloidogenic properties and structural characteristics based on the fuzzy oil drop model.
Related JoVE Video
Hydrophobic core formation in protein complex of cathepsin.
J. Biomol. Struct. Dyn.
PUBLISHED: 07-05-2013
Show Abstract
Hide Abstract
The "fuzzy oil drop" model assumes that the idealized hydrophobic core in a protein body can be described by a 3D Gauss function. The structure of the 1ICF protein (cathepsin), which participates in the proteolysis process and has cysteine-type peptidase activity, has been analyzed on the basis of the "fuzzy oil drop" model. The authors have determined the contribution of individual exon fragments to the creation of a common hydrophobic core and assessed the involvement of each chain in this process, depending on the number of complexed chains. Quantitative assessment of exons, chains, dimers, and the whole complex suggest that each of these units plays a different role in shaping the proteins hydrophobic core.
Related JoVE Video
Structural role of exon-coded fragment of polypeptide chains in selected enzymes.
J. Theor. Biol.
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
This paper discusses the structural role of fragments encoded by individual exons in proteins. Selected enzymes (hydrolases, transferases, ligases) reveal the presence of at least one exon fragment whose contribution to the proteins hydrophobic core is in line with theoretical expectations. This phenomenon is confirmed by quantitative analysis of the hydrophobicity density distribution in protein molecules. Results are compared with a 3D Gaussian function, treated as an "idealized" distribution of hydrophobicity density, with the highest values observed near the center of the molecule and near-zero values on its surface. At least one accordant exon fragment has been identified in each of the proteins subjected to analysis. On the basis of these results the authors propose that accordant exons are responsible for tertiary structural stabilization of proteins by ensuring the generation of a stable hydrophobic core.
Related JoVE Video
The use of supramolecular structures as protein ligands.
J Mol Model
PUBLISHED: 01-08-2013
Show Abstract
Hide Abstract
Congo red dye as well as other eagerly self-assembling organic molecules which form rod-like or ribbon-like supramolecular structures in water solutions, appears to represent a new class of protein ligands with possible wide-ranging medical applications. Such molecules associate with proteins as integral clusters and preferentially penetrate into areas of low molecular stability. Abnormal, partly unfolded proteins are the main binding target for such ligands, while well packed molecules are generally inaccessible. Of particular interest is the observation that local susceptibility for binding supramolecular ligands may be promoted in some proteins as a consequence of function-derived structural changes, and that such complexation may alter the activity profile of target proteins. Examples are presented in this paper.
Related JoVE Video
Hypothetical in silico model of the early-stage intermediate in protein folding.
J Mol Model
PUBLISHED: 01-07-2013
Show Abstract
Hide Abstract
This paper presents a method for determining the structure of the early stage (ES) intermediate in the multistage protein folding process. ES structure is modeled on the basis of a limited conformational subspace of the Ramachandran plot. The model distinguishes seven structural motifs corresponding to seven local probability maxima within the limited conformational subspace. Three of these are assigned to well-defined secondary structures, while the remaining four are found to represent various types of random coils. The presented heuristic approach also provides insight into the reasons behind incorrect predictions occurring when the folding process depends on external factors (e.g., ligands, ions or other proteins) rather than on the characteristics of the backbone itself. The accuracy of the presented method is estimated at around 48 %.
Related JoVE Video
Influence of the electric field on supramolecular structure and properties of amyloid-specific reagent Congo red.
Eur. Biophys. J.
PUBLISHED: 07-21-2011
Show Abstract
Hide Abstract
Among specific amyloid ligands, Congo red and its analogues are often considered potential therapeutic compounds. However, the results of the studies so far have not been univocal because the properties of this dye, derived mostly from its supramolecular nature, are still poorly understood. The supramolecular structure of Congo red, formed by ?-? stacking of dye molecules, is susceptible to the influence of the electric field, which may significantly facilitate electron delocalization. Consequently, the electric field may generate altered physico-chemical properties of the dye. Enhanced electron delocalization, induced by the electric field, alters the total charge of Congo red, making the dye more acidic (negatively charged). This is a consequence of withdrawing electrons from polar substituents of aromatic rings-sulfonic and amino groups-thus increasing their tendency to dissociate protons. The electric field-induced charge alteration observed in electrophoresis depends on dye concentration. This concentration-dependent charge alteration effect disappears when the supramolecular structure disintegrates in DMSO. Dipoles formed from supramolecular fibrillar species in the electric field become ordered in the solution, introducing the modified arrangement to liquid crystalline phase. Experimental results and theoretical studies provide evidence confirming predictions that the supramolecular character of Congo red is the main reason for its specific properties and reactivity.
Related JoVE Video
Internal force field in proteins seen by divergence entropy.
Bioinformation
PUBLISHED: 05-28-2011
Show Abstract
Hide Abstract
The characteristic distribution of non-binding interactions in a protein is described. It establishes that hydrophobic interactions can be characterized by suitable 3D Gauss functions while electrostatic interactions generally follow a random distribution. The implementation of this observation suggests differentiated optimization procedure for these two types of interactions. The electrostatic interaction may follow traditional energy optimization while the criteria for convergence shall measure the accordance with 3-D Gauss function.
Related JoVE Video
Intermediates in the protein folding process: a computational model.
Int J Mol Sci
PUBLISHED: 04-07-2011
Show Abstract
Hide Abstract
The paper presents a model for simulating the protein folding process in silico. The two-step model (which consists of the early stage-ES and the late stage-LS) is verified using two proteins, one of which is treated (according to experimental observations) as the early stage and the second as an example of the LS step. The early stage is based solely on backbone structural preferences, while the LS model takes into account the water environment, treated as an external hydrophobic force field and represented by a 3D Gauss function. The characteristics of 1ZTR (the ES intermediate, as compared with 1ENH, which is the LS intermediate) confirm the link between the gradual disappearance of ES characteristics in LS structural forms and the simultaneous emergence of LS properties in the 1ENH protein. Positive verification of ES and LS characteristics in these two proteins (1ZTR and 1ENH respectively) suggest potential applicability of the presented model to in silico protein folding simulations.
Related JoVE Video
Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants.
J Mol Model
PUBLISHED: 03-07-2011
Show Abstract
Hide Abstract
Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with "fuzzy oil drop" model was selected for analysis.
Related JoVE Video
"Fuzzy oil drop" model verified positively.
Bioinformation
PUBLISHED: 02-07-2011
Show Abstract
Hide Abstract
The "fuzzy oil drop" model assuming the structure of the hydrophobic core of the form of 3-D Gauss function appeared to be verified positively. The protein 1NMF belonging to downhill proteins was found to represent the hydrophobic density distribution accordant with the assumed model. The accordance of the protein structure with the assumed model was measured using elements of theory information. This observation opens the possibility to simulate the folding process as influenced by external force field of hydrophobic character.
Related JoVE Video
Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction.
J. Comput. Aided Mol. Des.
PUBLISHED: 08-05-2010
Show Abstract
Hide Abstract
The comparison of eight tools applicable to ligand-binding site prediction is presented. The methods examined cover three types of approaches: the geometrical (CASTp, PASS, Pocket-Finder), the physicochemical (Q-SiteFinder, FOD) and the knowledge-based (ConSurf, SuMo, WebFEATURE). The accuracy of predictions was measured in reference to the catalytic residues documented in the Catalytic Site Atlas. The test was performed on a set comprising selected chains of hydrolases. The results were analysed with regard to size, polarity, secondary structure, accessible solvent area of predicted sites as well as parameters commonly used in machine learning (F-measure, MCC). The relative accuracies of predictions are presented in the ROC space, allowing determination of the optimal methods by means of the ROC convex hull. Additionally the minimum expected cost analysis was performed. Both advantages and disadvantages of the eight methods are presented. Characterization of protein chains in respect to the level of difficulty in the active site prediction is introduced. The main reasons for failures are discussed. Overall, the best performance offers SuMo followed by FOD, while Pocket-Finder is the best method among the geometrical approaches.
Related JoVE Video
"Fuzzy oil drop" model applied to individual small proteins built of 70 amino acids.
J Mol Model
PUBLISHED: 01-19-2010
Show Abstract
Hide Abstract
The proteins composed of short polypeptides (about 70 amino acid residues) representing the following functional groups (according to PDB notation): growth hormones, serine protease inhibitors, antifreeze proteins, chaperones and proteins of unknown function, were selected for structural and functional analysis. Classification based on the distribution of hydrophobicity in terms of deficiency/excess as the measure of structural and functional specificity is presented. The experimentally observed distribution of hydrophobicity in the protein body is compared to the idealized one expressed by a three-dimensional Gauss function. The differences between these two distributions reveal the specificity of structural/functional characteristics of the protein. The residues of hydrophobicity deficiency versus the idealized distribution are assumed to indicate cavities with the potential to bind ligands, while the residues of hydrophobicity excess are interpreted as potentially participating in protein-protein complexation. The distribution of hydrophobicity irregularity seems to be specific for particular structures and functions of proteins. A comparative analysis of such profiles is carried out to identify the potential biological activity of proteins of unknown function.
Related JoVE Video
In silico structural study of random amino acid sequence proteins not present in nature.
Chem. Biodivers.
PUBLISHED: 12-19-2009
Show Abstract
Hide Abstract
The three-dimensional structures of a set of never born proteins (NBP, random amino acid sequence proteins with no significant homology with known proteins) were predicted using two methods: Rosetta and the one based on the fuzzy-oil-drop (FOD) model. More than 3000 different random amino acid sequences have been generated, filtered against the non redundant protein sequence data base, to remove sequences with significant homology with known proteins, and subjected to three-dimensional structure prediction. Comparison between Rosetta and FOD predictions allowed to select the ten top (highest structural similarity) and the ten bottom (the lowest structural similarity) structures from the ranking list organized according to the RMS-D value. The selected structures were taken for detailed analysis to define the scale of structural accordance and discrepancy between the two methods. The structural similarity measurements revealed discrepancies between structures generated on the basis of the two methods. Their potential biological function appeared to be quite different as well. The ten bottom structures appeared to be unfoldable for the FOD model. Some aspects of the general characteristics of the NBPs are also discussed. The calculations were performed on the EUChinaGRID grid platform to test the performance of this infrastructure for massive protein structure predictions.
Related JoVE Video
Serum albumin complexation of acetylsalicylic acid metabolites.
Curr. Drug Metab.
PUBLISHED: 08-20-2009
Show Abstract
Hide Abstract
One possible origin of the type I hypersensitivity reaction is reaction of drugs such as acetylsalicylic acid and its metabolites being complexed with human serum albumin. Albumin, being transporting molecule abundant in blood plasma is able to bind large array of ligands varying from small single carbon particles to long hydrophobic tailed lipidic acids (e.g. myristic acid). This non specificity is possible because of multi domain scaffold and large flexibility of inter-domain loops, which results in serious reorientation of domains. Hypothesis that acetylsalicylic acid metabolites may play indirect role in activation of allergic reaction has been tested. Binding of acetylsalicylic acid metabolites in intra-domain space causes significant increase of liability of domains IIIA and IIIB. One of metabolites, salicyluric acid, once is bound causes distortion and partial unfolding of helices in domains IA, IIB and IIIB. Changed are both directions and amplitude of relative motions as well as intra-domain distances. In result albumin is able to cross-link of adjacent IgE receptors which subsequently starts allergic reaction.
Related JoVE Video
Recognition of protein complexation based on hydrophobicity distribution.
Bioinformation
PUBLISHED: 08-04-2009
Show Abstract
Hide Abstract
The identification of the surface area able to generate the protein-protein complexation ligand and ion ligation is critical for the recognition of the biological function of particular proteins. The technique based on the analysis of the irregularity of hydrophobicity distribution is used as the criterion for the recognition of the interaction regions. Particularly, the exposure of hydrophobic residues on the surface of protein as well as the localization of the hydrophilic residues in the hydrophobic core is treated as potential area ready to interact with external molecules. The model based on the "fuzzy oil drop" approach treating the protein molecule as the drop of hydrophobicity concentrated in the central part of structure with the hydrophobicity close to zero on the surface according to 3-dimensional Gauss function. The comparison with the observed hydrophobicy in particular protein reveals some irregularities. These irregularities seem to represent the aim-oriented localization.
Related JoVE Video
Application of the fuzzy-oil-drop model to membrane protein simulation.
Proteins
PUBLISHED: 05-21-2009
Show Abstract
Hide Abstract
The analysis of structural properties and biological activity of membrane proteins requires long lasting simulation of molecular dynamics. The large number of atoms present in protein molecule, membrane (phospholipids), and water environment makes the simulation of large scale. The implementation of simplified model representing the natural environment for membrane proteins is presented and compared with the vacuum simulation and simulation in the presence of water molecules and membrane phospholipids presented explicite. The comparative structural analysis and computational times for these three models makes the simplified model promising.
Related JoVE Video
Functional characteristics of small proteins (70 amino acid residues) forming protein-nucleic acid complexes.
J. Biomol. Struct. Dyn.
PUBLISHED: 04-24-2009
Show Abstract
Hide Abstract
The proteins composed of short polypeptides (about 70 amino acid residues) participating in large complexes (ribosome) and proteins interacting with DNA/RNA were taken for analysis and classified according to the hydrophobicity excess/deficiency distribution as a measure of structural and functional specificity and similarity. The characterization of this group of proteins is the introductory part to the analysis of the so called "Never Born Proteins" (NBP) in search for protein compounds exhibiting biological activity that may be valuable in pharmacological research. The entropy scale (classification between random and deterministic limits) organized in ranking list allows the comparative analysis of the proteins under consideration. The comparison of the hydrophobicity deficiency appeared to be useful for similarity recognition, the examples of which are shown in the paper. The specificity of proteins participating in large protein-nucleic acid complexes generation is presented.
Related JoVE Video
Chaperonin structure: the large multi-subunit protein complex.
Int J Mol Sci
PUBLISHED: 02-09-2009
Show Abstract
Hide Abstract
The multi sub-unit protein structure representing the chaperonins group is analyzed with respect to its hydrophobicity distribution. The proteins of this group assist protein folding supported by ATP. The specific axial symmetry GroEL structure (two rings of seven units stacked back to back - 524 aa each) and the GroES (single ring of seven units - 97 aa each) polypeptide chains are analyzed using the hydrophobicity distribution expressed as excess/deficiency all over the molecule to search for structure-to-function relationships. The empirically observed distribution of hydrophobic residues is confronted with the theoretical one representing the idealized hydrophobic core with hydrophilic residues exposure on the surface. The observed discrepancy between these two distributions seems to be aim-oriented, determining the structure-to-function relation. The hydrophobic force field structure generated by the chaperonin capsule is presented. Its possible influence on substrate folding is suggested.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.