MSOP1016 QSAR Lecture 8&9 Summary

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What type of parameters are used to build a QSAR model?

Biological parameters

Hydrophobic parameters (correct)

Chemical parameters

Physical parameters

In a QSAR study, what type of analysis is commonly used to develop models?

Multiple regression analysis (correct)

Discriminant analysis

Cluster analysis

Factor analysis

What technique is used for screening molecules in virtual screening?

Enzyme kinetics

Immunofluorescence

Drug-receptor docking (correct)

Mass spectrometry

When is QSAR typically used in drug discovery?

When the molecular structure and properties of ligands are known Signup and view all the answers

Which parameter is NOT considered in building QSAR models?

Biological parameters Signup and view all the answers

What is one of the primary purposes of virtual combinatorial chemistry methods?

Screening diverse set of molecules Signup and view all the answers

What relationship exists between hydrophobicity constant (π) and the hydrophobicity of a substituent?

A positive π value indicates the substituent is more hydrophobic than H Signup and view all the answers

How can hydrophobic parameters be used to predict drug activity?

Most drugs need to be hydrophobic to be absorbed, so hydrophobic parameters are crucial Signup and view all the answers

What type of relationship do linear QSAR logP examples demonstrate?

As logP increases, binding to proteins increases Signup and view all the answers

How do electron parameters contribute to drug-receptor interactions?

They measure electrostatic interaction forces between molecules in drug-receptor interactions Signup and view all the answers

What effect does increasing logP have on the hypnosis effect of barbiturates according to parabolic relationships?

Hypnosis effect reaches a maximum at an optimum logP value, then decreases Signup and view all the answers

What is the significance of the hydrophobicity constant (π) in calculating octanol/water partition coefficients?

π values are used to adjust log P values in different solvent systems Signup and view all the answers

What is the main aim of using QSAR in predicting biological activity?

To express the relationship between chemical structure and biological activity mathematically Signup and view all the answers

What is one main requirement for building a QSAR model?

Having a diverse set of drug molecules Signup and view all the answers

What does QSAR stand for?

Quantitative Structure-Activity Relationship Signup and view all the answers

In QSAR, what is used to represent the 2D structure of a compound for computer calculations?

SMILES codes Signup and view all the answers

Which term is used to refer to the statistical relationships between molecular structure and biological activity?

Quantitative Structure-Activity Relationship (QSAR) Signup and view all the answers

What is the purpose of determining properties like molecular weight and polarity in QSAR?

To quantify the molecular structure for correlation analysis Signup and view all the answers

How is the relationship between chemical structure and biological activity expressed in QSAR?

$y = c + mx$ Signup and view all the answers

Why might there be errors in predicting biological activity using QSAR models?

Because the line of best fit may not perfectly represent all data points Signup and view all the answers

What does Log P represent in QSAR calculations?

A molecular property used to calculate relationships in QSAR Signup and view all the answers

Which scientist is primarily credited with developing the methodology known as QSAR?

Corwin Hansch Signup and view all the answers

What role do shape and size play in biological activity?

Impact the absorption of large compounds Signup and view all the answers

In a drug-receptor interaction, what effect does steric hindrance from a substituent have?

Decreases affinity Signup and view all the answers

What is the simplest molecular parameter related to size?

Molecular volume Signup and view all the answers

Which parameter describes the volume occupied by one mole of a compound?

Molecular volume Signup and view all the answers

What does a high correlation coefficient (r) indicate in QSAR models?

Goodness of fit Signup and view all the answers

What information is provided by the standard error of the estimate (s) in a QSAR model?

Error value Signup and view all the answers

What does an r2 value of 0.96 represent in QSAR models?

"Percent of variation explained by X" Signup and view all the answers

In a QSAR study, what does log(1/EC50) = 0.817π - 0.764 represent?

"Regression equation" Signup and view all the answers

"Log Biologic activity = Log P" suggests a correlation between what two parameters?

"Biologic activity and hydrophobicity" Signup and view all the answers

"Log 1/C = 0.75 Log P + 2.30" provides information on what aspect in a QSAR model?

"Regression equation" Signup and view all the answers

According to the provided equation, which substituents should be chosen to increase activity based on their effect on pi and sigma values?

Substituents with positive pi and negative sigma values Signup and view all the answers

In a QSAR study, which molecular descriptor would be associated with hydrophobicity according to the text?

Log P Signup and view all the answers

Which parameter is crucial for determining the goodness of fit for a QSAR equation in regression analysis?

Correlation coefficient, r/r2 Signup and view all the answers

When interpreting a QSAR equation, what type of substituents would be selected to increase activity based on their pi and sigma values?

Positive pi and negative sigma values Signup and view all the answers

What is the significance of SMILES encoding in the context of QSAR studies?

Encoding 2D chemical structures for molecular descriptor calculation Signup and view all the answers

In Craig plots, which areas correspond to hydrophobic/lipophilic and electron-donating substituents respectively?

Areas 2 and 4; Areas 3 and 4 Signup and view all the answers

What is the primary function of electron-deficient groups in morphine analogues?

Interact with a negatively charged area in the receptor site Signup and view all the answers

Which type of groups will reduce the electron density on the amine, leading to a stronger interaction with the receptor?

Electron-withdrawing groups Signup and view all the answers

What effect do electron-donating groups like methyl (-CH3) have on the affinity of morphine analogues?

Reduce the analgesic effect Signup and view all the answers

What is the purpose of the Hammett constant sigma (σ) introduced by Hammett?

Predict rate constants of chemical reactions Signup and view all the answers

In the context of Hammett constant sigma (σ), what do positive values indicate for substituents?

Strong electron-withdrawing ability Signup and view all the answers

How does an electron-donating group like -CH3 affect the pKa value of a compound compared to the parent compound?

Decrease the pKa value Signup and view all the answers

What is a key characteristic of Hammett constant sigma (σ) regarding its application in QSAR?

Always includes a hydrophobicity parameter Signup and view all the answers

What is the relationship between electron-withdrawing groups and biological activity according to Hammett constant sigma (σ) applications?

<ul> <li>positive σ leads to increased activity</li> </ul> Signup and view all the answers

How does Hammett constant sigma (σ) define the order of activity in methadone analogues?

-NO2 > Cl > H > CH3 Signup and view all the answers

What is one of the key roles of hydrogen bonding in molecular interactions?

Affects receptor binding Signup and view all the answers

What is the equation for multiple linear regression used in QSAR?

Log 1/EC50 = 0.398+1.089 +1.03MW +4.541 Signup and view all the answers

How many descriptors are needed in a QSAR model according to the content provided?

At least 2 descriptors Signup and view all the answers

What does a positive coefficient for parameter 𝜋 signify in a QSAR equation?

Increases biological activity Signup and view all the answers

Why is it important to split chemicals into training and test sets in QSAR modeling?

To validate the predictive power of the model Signup and view all the answers

What does the statement 'Rubbish in, Rubbish out' imply in the context of QSAR modeling?

Quality of input data impacts model outcomes Signup and view all the answers

Which term refers to Taft's steric parameter in QSAR modeling?

Es Signup and view all the answers

In a QSAR equation, what does a negative coefficient for parameter 𝜎 suggest?

Decreases biological activity Signup and view all the answers

How is the success of a QSAR model influenced by the number of compounds used?

More compounds lead to more accurate predictions Signup and view all the answers

'Craig Plots' are primarily used for what purpose in QSAR modeling?

'Quickly deciding which analogs to synthesize' Signup and view all the answers

'MLR analysis' in QSAR stands for what term?

'Multiple Linear Regression' Signup and view all the answers

What does logP represent as a molecular descriptor in QSAR studies?

Hydrophobicity of the molecule Signup and view all the answers

Which descriptor is significant for drug-receptor binding according to the text?

Polarizability Signup and view all the answers

What can be deduced from a small range of logP values for a molecule according to the text?

A linear relationship between log 1/C and log P Signup and view all the answers

What is the significance of logP for passing through membranes?

It represents hydrophobicity for passing through membranes Signup and view all the answers

Which parameter dominates when logP values are small in QSAR studies?

Log P term Signup and view all the answers

In QSAR studies, what happens to activity as logP increases beyond a certain point?

Activity first increases then decreases Signup and view all the answers

Why might a molecule with high logP values be more susceptible to metabolism?

Due to decreased solubility in aqueous phase Signup and view all the answers

What is the relationship between log 1/C and log P when graphed at very high logP values?

'A parabolic curve' Signup and view all the answers

'Over a small range of log P, e.g. logP 1-4, a straight line is obtained' - this statement indicates a linear relationship between what variables?

'Log 1/C and log P' Signup and view all the answers

'When log P large, log P squared dominates & so activity decreases' - this statement explains the influence of what on biological activity?

Increased log P Signup and view all the answers