Podcast
Questions and Answers
Binding sites for macromolecules are generally flatter than binding sites for small molecules.
Binding sites for macromolecules are generally flatter than binding sites for small molecules.
True
DNA binding sites are characterized by negative charged electrostatic patches.
DNA binding sites are characterized by negative charged electrostatic patches.
False
Knowledge-based methods for identifying binding sites rely solely on evolutionary conservation.
Knowledge-based methods for identifying binding sites rely solely on evolutionary conservation.
False
High evolutionary conservation is a typical feature of binding sites for macromolecules.
High evolutionary conservation is a typical feature of binding sites for macromolecules.
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Meta-servers are tools that utilize a single method to identify binding sites.
Meta-servers are tools that utilize a single method to identify binding sites.
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Solvent accessible surface area (SASA) is measured in Å2 and indicates the extent to which a residue in a protein is accessible to the solvent.
Solvent accessible surface area (SASA) is measured in Å2 and indicates the extent to which a residue in a protein is accessible to the solvent.
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The term 'solvent excluded surface' is synonymous with the molecular surface and does not provide any visual representation.
The term 'solvent excluded surface' is synonymous with the molecular surface and does not provide any visual representation.
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The relative accessible surface area (rASA) is calculated using the formula rASA = ASA + ASAMAX.
The relative accessible surface area (rASA) is calculated using the formula rASA = ASA + ASAMAX.
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The radius of the spherical probe used to calculate SASA is approximately 1.4 Å, which is the typical water radius.
The radius of the spherical probe used to calculate SASA is approximately 1.4 Å, which is the typical water radius.
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The simplified two-state description for residue accessibility only categorizes residues as either buried or buried.
The simplified two-state description for residue accessibility only categorizes residues as either buried or buried.
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Molecular surface visualization reflects the solvent excluded surface, which is an important consideration in protein modeling.
Molecular surface visualization reflects the solvent excluded surface, which is an important consideration in protein modeling.
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An increase in solvent accessible surface area (SASA) generally corresponds to a decrease in the residue's exposure to the solvent.
An increase in solvent accessible surface area (SASA) generally corresponds to a decrease in the residue's exposure to the solvent.
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Both SASA and SES are important for understanding protein interactions with their environment.
Both SASA and SES are important for understanding protein interactions with their environment.
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The bottleneck in a tunnel or channel refers to the widest part, which is crucial for selectivity.
The bottleneck in a tunnel or channel refers to the widest part, which is crucial for selectivity.
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Voronoi diagrams are utilized to identify the optimal pathways connecting starting points with the bulk solvent.
Voronoi diagrams are utilized to identify the optimal pathways connecting starting points with the bulk solvent.
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Geometry-based methods for pocket detection generally provide extensive information on the characteristics of tunnels and channels.
Geometry-based methods for pocket detection generally provide extensive information on the characteristics of tunnels and channels.
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Molecular recognition involves specific interactions between molecules through covalent bonding.
Molecular recognition involves specific interactions between molecules through covalent bonding.
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Transport pathways primarily facilitate the transport of large biomolecules such as proteins and nucleic acids.
Transport pathways primarily facilitate the transport of large biomolecules such as proteins and nucleic acids.
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Identification methods for channels in proteins analyze multiple channels simultaneously within the structure.
Identification methods for channels in proteins analyze multiple channels simultaneously within the structure.
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Dijkstra’s algorithm is used to identify tunnels by optimizing pathways based on defined cost functions.
Dijkstra’s algorithm is used to identify tunnels by optimizing pathways based on defined cost functions.
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Tunnels allow for the transport of reaction intermediates in monofunctional enzymes.
Tunnels allow for the transport of reaction intermediates in monofunctional enzymes.
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The probe size in tunnel identification specifies the maximum radius threshold for the search.
The probe size in tunnel identification specifies the maximum radius threshold for the search.
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Channels and tunnels can be differentiated based on whether they connect occluded cavities with the protein surface.
Channels and tunnels can be differentiated based on whether they connect occluded cavities with the protein surface.
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Druggability refers to the likelihood of a protein being targeted by a drug-like molecule leading to a therapeutic effect.
Druggability refers to the likelihood of a protein being targeted by a drug-like molecule leading to a therapeutic effect.
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Lipinski’s rule of 5 states that a drug should have a molecular weight of no more than 1000 Da.
Lipinski’s rule of 5 states that a drug should have a molecular weight of no more than 1000 Da.
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One can predict protein druggability exclusively by using the sequence of the entire protein.
One can predict protein druggability exclusively by using the sequence of the entire protein.
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The Cambridge Structural Database is a resource for small molecule representation.
The Cambridge Structural Database is a resource for small molecule representation.
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PockDrug Server and DoGSiteScorer are examples of predictive tools used for determining protein druggability.
PockDrug Server and DoGSiteScorer are examples of predictive tools used for determining protein druggability.
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In 2D molecular representation, a chemical structure can be depicted using SMILES notation.
In 2D molecular representation, a chemical structure can be depicted using SMILES notation.
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It is acceptable for small molecules to have no protonation states.
It is acceptable for small molecules to have no protonation states.
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A violation of Lipinski’s rule of 5 means a drug must strictly adhere to all the parameters without exceptions.
A violation of Lipinski’s rule of 5 means a drug must strictly adhere to all the parameters without exceptions.
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Enzymes increase the speed of chemical reactions by increasing the activation barrier.
Enzymes increase the speed of chemical reactions by increasing the activation barrier.
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The Arrhenius equation demonstrates that a lower activation energy results in a higher kinetic rate.
The Arrhenius equation demonstrates that a lower activation energy results in a higher kinetic rate.
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Molecular recognition requires complementarity between the ligand and both the active site and the tunnel.
Molecular recognition requires complementarity between the ligand and both the active site and the tunnel.
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PDBbind is a database that contains unverified information about molecular complexes.
PDBbind is a database that contains unverified information about molecular complexes.
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The formation of the enzyme-substrate complex is a step in the reaction process that leads to products.
The formation of the enzyme-substrate complex is a step in the reaction process that leads to products.
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A buried active site in a receptor does not require tunnels for ligand binding.
A buried active site in a receptor does not require tunnels for ligand binding.
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Experimentally determined complexes are available in the RSCB PDB database.
Experimentally determined complexes are available in the RSCB PDB database.
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The term 'transition state' refers to the state of the system where the energy is at its minimum.
The term 'transition state' refers to the state of the system where the energy is at its minimum.
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Molecular docking methods can be useful even when experimental data is not available.
Molecular docking methods can be useful even when experimental data is not available.
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Receptor representation in molecular docking only requires knowledge of the entire protein structure.
Receptor representation in molecular docking only requires knowledge of the entire protein structure.
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Soft docking employs rigid scoring functions to simulate the flexibility of receptors.
Soft docking employs rigid scoring functions to simulate the flexibility of receptors.
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Ligand representation always includes all atoms, without any exceptions.
Ligand representation always includes all atoms, without any exceptions.
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The complexity of ligand conformational space increases with the number of rotatable bonds.
The complexity of ligand conformational space increases with the number of rotatable bonds.
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Search algorithms for molecular docking can operate under completely flexible docking conditions without constraints.
Search algorithms for molecular docking can operate under completely flexible docking conditions without constraints.
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Geometry-based algorithms rely solely on the similarity of shape between the receptor and ligand.
Geometry-based algorithms rely solely on the similarity of shape between the receptor and ligand.
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Scoring functions must provide an inefficient and detailed description of protein-ligand interactions.
Scoring functions must provide an inefficient and detailed description of protein-ligand interactions.
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Empirical and force field-based scoring functions are two categories of scoring functions used in molecular docking.
Empirical and force field-based scoring functions are two categories of scoring functions used in molecular docking.
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Intermolecular interactions in the evaluation of complexes do not include ionic interactions.
Intermolecular interactions in the evaluation of complexes do not include ionic interactions.
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Transportation of small molecules through tunnels can only be analyzed using molecular docking methods.
Transportation of small molecules through tunnels can only be analyzed using molecular docking methods.
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Molecular docking can employ stochastic algorithms that require multiple, independent runs for consistent results.
Molecular docking can employ stochastic algorithms that require multiple, independent runs for consistent results.
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The optimization of receptor flexibility may involve rotating the entire protein structure.
The optimization of receptor flexibility may involve rotating the entire protein structure.
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CaverDock and MoMA-LigPath are based on force field methods and provide high accuracy.
CaverDock and MoMA-LigPath are based on force field methods and provide high accuracy.
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Ligandability must be present for druggability but it is not a sufficient condition.
Ligandability must be present for druggability but it is not a sufficient condition.
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Template-based methods for identifying binding sites use 2D representations of the proteins.
Template-based methods for identifying binding sites use 2D representations of the proteins.
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Knowledge-based methods for predicting binding sites involve the evaluation of local environments such as residue types and their distances.
Knowledge-based methods for predicting binding sites involve the evaluation of local environments such as residue types and their distances.
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The construction of 3D templates in template-based methods allows for the characterization of binding sites solely on geometric shape.
The construction of 3D templates in template-based methods allows for the characterization of binding sites solely on geometric shape.
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Identification of potential binding sites in the query structure is done by comparing it against a 2D template database.
Identification of potential binding sites in the query structure is done by comparing it against a 2D template database.
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Solvent accessible surface area (SASA) is always represented in square meters.
Solvent accessible surface area (SASA) is always represented in square meters.
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The radius of the spherical probe used to calculate SASA is approximately the Van der Waals radius.
The radius of the spherical probe used to calculate SASA is approximately the Van der Waals radius.
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Relative accessible surface area (rASA) allows for comparing the accessibility of different types of residues.
Relative accessible surface area (rASA) allows for comparing the accessibility of different types of residues.
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Solvent excluded surface (SES) is also referred to as the molecular surface but is usually represented in volumetric terms.
Solvent excluded surface (SES) is also referred to as the molecular surface but is usually represented in volumetric terms.
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A simplified two-state description categorizes residues strictly as either buried or exposed based on accessibility.
A simplified two-state description categorizes residues strictly as either buried or exposed based on accessibility.
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The term 'solvent excluded surface' refers to the area of a residue that cannot be accessed by water molecules.
The term 'solvent excluded surface' refers to the area of a residue that cannot be accessed by water molecules.
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Long extended amino acids have a significantly lower rASA compared to spherical amino acids.
Long extended amino acids have a significantly lower rASA compared to spherical amino acids.
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The calculation of solvent accessible surface area involves summing the area accessible by a rigid probe across the protein structure.
The calculation of solvent accessible surface area involves summing the area accessible by a rigid probe across the protein structure.
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The lock-and-key model proposes that both ligand and receptor are flexible and can adjust their shapes.
The lock-and-key model proposes that both ligand and receptor are flexible and can adjust their shapes.
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The induced-fit model allows for only partial complementarity between the ligand and receptor during complex formation.
The induced-fit model allows for only partial complementarity between the ligand and receptor during complex formation.
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The selected-fit model, proposed by B.F. Straub, indicates that the bound conformation of the receptor exists only when the ligand is attached.
The selected-fit model, proposed by B.F. Straub, indicates that the bound conformation of the receptor exists only when the ligand is attached.
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Allosteric mechanisms are adequately explained by the lock-and-key model of molecular recognition.
Allosteric mechanisms are adequately explained by the lock-and-key model of molecular recognition.
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The keyhole-lock-key model maintains that conformations of both ligand and receptor are strictly defined and do not exhibit flexibility.
The keyhole-lock-key model maintains that conformations of both ligand and receptor are strictly defined and do not exhibit flexibility.
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Enzymes decrease the activation barrier, which increases the kinetic rate of reactions.
Enzymes decrease the activation barrier, which increases the kinetic rate of reactions.
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The transition state represents the state of the system where the energy is at its maximum.
The transition state represents the state of the system where the energy is at its maximum.
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Tunnels serve as barriers that prevent reaction intermediates from passing through enzymes.
Tunnels serve as barriers that prevent reaction intermediates from passing through enzymes.
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The bottleneck in a tunnel or channel refers to the narrowest part, which is crucial for selectivity.
The bottleneck in a tunnel or channel refers to the narrowest part, which is crucial for selectivity.
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Molecular recognition takes place solely based on the shape complementarity between molecules.
Molecular recognition takes place solely based on the shape complementarity between molecules.
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The PDBbind database is a collection of verified data about molecular complexes.
The PDBbind database is a collection of verified data about molecular complexes.
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Tunnels in proteins can facilitate the transport of reaction intermediates only between active sites in bifunctional enzymes.
Tunnels in proteins can facilitate the transport of reaction intermediates only between active sites in bifunctional enzymes.
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Identification methods for tunnels typically analyze multiple tunnels simultaneously within the protein structure.
Identification methods for tunnels typically analyze multiple tunnels simultaneously within the protein structure.
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Complementarity with the ligand is important for both the active site and the tunnel of a receptor.
Complementarity with the ligand is important for both the active site and the tunnel of a receptor.
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Experimentally determined structures of complexes can be found in the Cambridge Structural Database.
Experimentally determined structures of complexes can be found in the Cambridge Structural Database.
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Voronoi diagrams are utilized to visualize the skeleton of voids among atoms, but they do not assist in calculating optimal pathways.
Voronoi diagrams are utilized to visualize the skeleton of voids among atoms, but they do not assist in calculating optimal pathways.
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Lowering the activation energy directly results in a higher rate constant according to the Arrhenius equation.
Lowering the activation energy directly results in a higher rate constant according to the Arrhenius equation.
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The geometry-based methods for pocket detection provide extensive information on the characteristics of the tunnels and channels they identify.
The geometry-based methods for pocket detection provide extensive information on the characteristics of the tunnels and channels they identify.
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The probe size used in tunnel identification establishes a maximum radius threshold for identifying potential tunnels.
The probe size used in tunnel identification establishes a maximum radius threshold for identifying potential tunnels.
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Molecular recognition processes occur exclusively through covalent bonding between molecules.
Molecular recognition processes occur exclusively through covalent bonding between molecules.
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Methods for identifying channels do not provide information about tunnels leading from occluded cavities.
Methods for identifying channels do not provide information about tunnels leading from occluded cavities.
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Dijkstra’s algorithm is employed to identify channels by optimizing pathway criteria based on cost functions.
Dijkstra’s algorithm is employed to identify channels by optimizing pathway criteria based on cost functions.
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An essential aspect of molecular recognition is the specific interactions that can occur between ligands and both active sites and tunnels.
An essential aspect of molecular recognition is the specific interactions that can occur between ligands and both active sites and tunnels.
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Molecular docking is primarily useful when experimental data is unavailable.
Molecular docking is primarily useful when experimental data is unavailable.
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Ligands are always represented by all their atoms in molecular docking.
Ligands are always represented by all their atoms in molecular docking.
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Soft docking uses rigid scoring functions to simulate receptor flexibility.
Soft docking uses rigid scoring functions to simulate receptor flexibility.
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The energy-driven algorithms in molecular docking directly locate the global maximum of binding free energy.
The energy-driven algorithms in molecular docking directly locate the global maximum of binding free energy.
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Empirical, knowledge-based, and force field-based methods are the only categories of scoring functions in molecular docking.
Empirical, knowledge-based, and force field-based methods are the only categories of scoring functions in molecular docking.
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Rigid docking methods have more flexible constraints compared to fully flexible methods.
Rigid docking methods have more flexible constraints compared to fully flexible methods.
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Geometry-based algorithms for molecular docking operate under the assumption of physicochemical complementarity.
Geometry-based algorithms for molecular docking operate under the assumption of physicochemical complementarity.
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Intermolecular interactions, such as hydrogen bonds and ionic interactions, are crucial in the evaluation of molecular complexes.
Intermolecular interactions, such as hydrogen bonds and ionic interactions, are crucial in the evaluation of molecular complexes.
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Transport pathways for small molecules are solely based on high accuracy methods, like multiple MD simulations.
Transport pathways for small molecules are solely based on high accuracy methods, like multiple MD simulations.
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Scoring functions evaluate all binding modes from searching algorithms to rank potential ligand configurations.
Scoring functions evaluate all binding modes from searching algorithms to rank potential ligand configurations.
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Explicit side-chain flexibility involves optimizing the entire protein structure as a whole.
Explicit side-chain flexibility involves optimizing the entire protein structure as a whole.
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The representation of the receptor in molecular docking can include a grid representation covering the entire search region.
The representation of the receptor in molecular docking can include a grid representation covering the entire search region.
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Machine learning is not a category of scoring functions used in molecular docking assessment.
Machine learning is not a category of scoring functions used in molecular docking assessment.
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Residue solvent accessibility can be determined by rASA values outside the range of 15–25%.
Residue solvent accessibility can be determined by rASA values outside the range of 15–25%.
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Protein solubility refers to the concentration of protein that saturates the solution in a solid phase equilibrium.
Protein solubility refers to the concentration of protein that saturates the solution in a solid phase equilibrium.
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Intra-molecular interactions occur between different proteins in assemblies.
Intra-molecular interactions occur between different proteins in assemblies.
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Aggregation-prone regions (APRs) in proteins are mainly characterized by hydrophilic residues that avoid beta-structures.
Aggregation-prone regions (APRs) in proteins are mainly characterized by hydrophilic residues that avoid beta-structures.
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Charge-charge (ionic) interactions are exclusive to neutral residues in protein structures.
Charge-charge (ionic) interactions are exclusive to neutral residues in protein structures.
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Binding sites for macromolecules are typically identified through evolutionary and knowledge-based methods.
Binding sites for macromolecules are typically identified through evolutionary and knowledge-based methods.
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Macromolecule binding sites require small surface areas for effective recognition.
Macromolecule binding sites require small surface areas for effective recognition.
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Characterization of DNA binding sites includes the presence of negatively charged electrostatic patches.
Characterization of DNA binding sites includes the presence of negatively charged electrostatic patches.
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Knowledge-based methods exclusively rely on structural properties to identify macromolecule binding sites.
Knowledge-based methods exclusively rely on structural properties to identify macromolecule binding sites.
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High evolutionary conservation is a feature that distinguishes macromolecule binding sites from other types of binding sites.
High evolutionary conservation is a feature that distinguishes macromolecule binding sites from other types of binding sites.
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The lock-and-key model proposed by E. Fisher in 1894 considers both the ligand and receptor as flexible.
The lock-and-key model proposed by E. Fisher in 1894 considers both the ligand and receptor as flexible.
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The induced-fit model introduced by D.E. Koshland in 1956 requires only partial complementarity for molecular recognition.
The induced-fit model introduced by D.E. Koshland in 1956 requires only partial complementarity for molecular recognition.
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The selected-fit model, also known as conformational selection, suggests that both ligand and receptor must be rigid for a complex to form.
The selected-fit model, also known as conformational selection, suggests that both ligand and receptor must be rigid for a complex to form.
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The keyhole-lock-key model is another name for the selected-fit model in molecular recognition.
The keyhole-lock-key model is another name for the selected-fit model in molecular recognition.
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According to the selected-fit model, the conformation of the bound receptor exists in its free state.
According to the selected-fit model, the conformation of the bound receptor exists in its free state.
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Cation-π interactions occur between a positively charged residue and negatively charged residues.
Cation-π interactions occur between a positively charged residue and negatively charged residues.
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Hydrophobic interactions arise from entropic effects and are mainly significant for polar residues.
Hydrophobic interactions arise from entropic effects and are mainly significant for polar residues.
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Disulfide bonds are formed between two cysteine molecules through the sharing of hydrogen atoms.
Disulfide bonds are formed between two cysteine molecules through the sharing of hydrogen atoms.
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Aromatic stacking interactions involve repulsive forces between closely aligned aromatic residues.
Aromatic stacking interactions involve repulsive forces between closely aligned aromatic residues.
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Van der Waals interactions are only significant between charged atoms.
Van der Waals interactions are only significant between charged atoms.
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High-molecular weight molecules generally have a better chance of achieving medicinal druggability.
High-molecular weight molecules generally have a better chance of achieving medicinal druggability.
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Lipinski’s rule of 5 allows two violations in the parameters for orally-active drugs.
Lipinski’s rule of 5 allows two violations in the parameters for orally-active drugs.
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Molecular docking primarily focuses on the prediction of protein structures without regard to ligand interactions.
Molecular docking primarily focuses on the prediction of protein structures without regard to ligand interactions.
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The Cambridge Structural Database contains information regarding small molecule representations.
The Cambridge Structural Database contains information regarding small molecule representations.
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Identifying protein druggability can solely rely on the structural features of binding sites without considering similarity to known targets.
Identifying protein druggability can solely rely on the structural features of binding sites without considering similarity to known targets.
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A small molecule representation can be depicted in 1D form as an empirical formula.
A small molecule representation can be depicted in 1D form as an empirical formula.
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PockDrug Server and DoGSiteScorer are tools that assist in predicting protein druggability.
PockDrug Server and DoGSiteScorer are tools that assist in predicting protein druggability.
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Protonation states are irrelevant when discussing the preparation of small molecule structures.
Protonation states are irrelevant when discussing the preparation of small molecule structures.
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Molecular docking is useful when experimental data is not available or for virtual screening.
Molecular docking is useful when experimental data is not available or for virtual screening.
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Receptor representation in molecular docking must always include every atom of the receptor.
Receptor representation in molecular docking must always include every atom of the receptor.
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Ligand flexibility in molecular docking allows for rotation about multiple bonds simultaneously.
Ligand flexibility in molecular docking allows for rotation about multiple bonds simultaneously.
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Soft docking utilizes hard scoring functions to simulate receptor flexibility.
Soft docking utilizes hard scoring functions to simulate receptor flexibility.
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Many search algorithms for molecular docking are available, including fully flexible methods.
Many search algorithms for molecular docking are available, including fully flexible methods.
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Geometry-based algorithms in molecular docking assume binding is governed solely by interactions of physicochemical properties.
Geometry-based algorithms in molecular docking assume binding is governed solely by interactions of physicochemical properties.
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Scoring functions are essential for ranking different configurations of a ligand bound to a protein in molecular docking.
Scoring functions are essential for ranking different configurations of a ligand bound to a protein in molecular docking.
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Empirical and knowledge-based are the only categories of scoring functions in molecular docking.
Empirical and knowledge-based are the only categories of scoring functions in molecular docking.
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The evaluation of molecular complexes considers only binding energies, excluding intermolecular interactions.
The evaluation of molecular complexes considers only binding energies, excluding intermolecular interactions.
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Transport pathways in molecules can only be assessed through methods that utilize advanced MD simulations.
Transport pathways in molecules can only be assessed through methods that utilize advanced MD simulations.
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Hydrogen bonds and hydrophobic interactions are the only types of intermolecular interactions considered in the evaluation of complexes.
Hydrogen bonds and hydrophobic interactions are the only types of intermolecular interactions considered in the evaluation of complexes.
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Ligand fragment techniques in molecular docking involve docking the complete ligand as a whole.
Ligand fragment techniques in molecular docking involve docking the complete ligand as a whole.
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Molecular docking allows for the study of drug selectivity by evaluating one ligand bound to several different proteins.
Molecular docking allows for the study of drug selectivity by evaluating one ligand bound to several different proteins.
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Study Notes
Protein Structure Analysis
- Residue solvent accessibility measures the surface area of a residue in a protein accessible to solvent.
- Solvent accessible surface area (ASA/SASA/SAS) is measured in Ų.
- Residue solvent accessibility is calculated by rolling a spherical probe over the protein surface and summing the accessible area.
- Solvent excluded surface (SES) is also known as molecular surface or Connolly surface area.
- Relative accessible surface area (rASA) is the ratio of the actual accessible area of a residue to the maximum accessible area.
Protein Solubility
- Protein solubility is the concentration of protein in a saturated solution at equilibrium with the solid phase.
- Several factors affect protein solubility, including the balance of hydrophilic and hydrophobic residues and aggregation-prone regions (APRs).
- APRs mainly have hydrophobic residues that are prone to form beta-structures.
- Proteins expressed in a lab are influenced by multiple factors.
Molecular Interactions
- Intramolecular interactions occur within a protein structure.
- Intermolecular interactions occur between different proteins in assemblies.
- Molecular interactions are essential for understanding the function and stability of proteins and their complexes.
- Various types of interactions include charge-charge (ionic), hydrogen bonds, aromatic, Van der Waals (vdW) and hydrophobic interactions.
- Disulfide bonds (cysteine bridges), cation-π interactions, and polar interactions are also important.
Functional Sites
- Binding sites on a protein provide complementarity for a bound molecule (ligand).
- Active/catalytic sites promote chemical catalysis (breaking/forming covalent bonds).
- Binding involves non-covalent interactions between the protein and the ligand.
- Binding sites for small molecules are usually internal cavities, surface pockets or clefts.
- Binding sites are highly conserved by evolution, with low desolvation energy and characteristic physicochemical properties.
- Binding sites are also characterized by methods like evolutionary conservation, physical detection of "pockets," geometry based methods, energy based methods, knowledge based and template based methods.
Transport Pathways
- Transport pathways mediate the transport of ions and small molecules within proteins.
- These pathways are essential functions for many protein types.
- Channels/pores and tunnels are types of transport pathways.
- Intramolecular tunnels transport intermediates between different active sites in bifunctional enzymes.
- The permeability of a pathway depends on size, shape, amino acid composition (physicochemical properties) and dynamics.
- Identification of transport pathways involves identifying overall voids, tunnels and channels.
Protein-Ligand Complexes
- Molecular recognition refers to the specific interactions between two or more molecules through non-covalent bonding.
- Different biological roles include binding, catalysis and signaling.
- Several models can explain molecular recognition like: lock and key model, induced fit model and selected fit model.
- Keyhole-lock-key model is relevant when a receptor has active sites and tunnels.
Biocatalysis
- Enzymes increase chemical reaction speeds by decreasing the activation barrier.
- Enzymes provide environments that stabilize the transition state(s).
- Biocatalysis relates to kinetic rate and activation energy.
Structures of Complexes
- Experimentally determined complexes are found in databases like PDB, BindingDB, ChEMBL.
Protein Druggability
- Druggability is the likelihood of a protein being targeted or modulated by a drug.
- Drug-like molecules must bind to the protein with high affinity.
- Descriptors such as Lipinski's rule of 5 are used for drug candidates and prediction.
Small Molecules
- Small molecules are represented by 1D (empirical formulas), 2D (chemical structure diagrams) and 3D (atomic coordinates) models.
- Databases such as the Cambridge Structural Database, PubChem, and ZINC database are used.
Molecular Docking
- Molecular Docking is used when experimental data is unavailable for virtual screening.
- Several components/steps are involved in molecular docking which include receptor representation, ligand representation, search of binding modes, scoring.
- Several search algorithms are available such as rigid docking, semi-flexible and fully flexible.
- Several categories of scoring functions are employed including empirical, knowledge-based, force field based and machine-learning.
Evaluation of Complexes
- Intermolecular interactions are assessed in complexes, as well as binding energies.
Transport of Small Molecules
- Transport pathways are studied by examining both geometric and force field methods.
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Description
Test your knowledge on the characteristics and identification methods of binding sites for macromolecules. This quiz covers topics such as electrostatic patches, evolutionary conservation, and the use of meta-servers in binding site identification. Challenge yourself and see how well you understand these essential concepts in biochemistry.
