Podcast
Questions and Answers
What type of properties can be mapped onto the surface of a molecule using colours in molecular modelling?
What type of properties can be mapped onto the surface of a molecule using colours in molecular modelling?
- Physical properties only
- Non-physical properties only
- Both physical and non-physical properties (correct)
- Chemical properties only
Which method in computational chemistry is known for its simplicity but less accuracy compared to quantum mechanics?
Which method in computational chemistry is known for its simplicity but less accuracy compared to quantum mechanics?
- Molecular mechanics (correct)
- Semiempirical methods
- Quantum mechanics
- Empirical force fields
What is the primary purpose of quantum mechanics in computational chemistry?
What is the primary purpose of quantum mechanics in computational chemistry?
- To estimate experiment results accurately (correct)
- To calculate energy and kinetic forms of energy
- To visualize non-physical properties of molecules
- To map physical properties of molecules in colors
Which energy forms are considered for a penicillin molecule interacting with a penicillin receptor?
Which energy forms are considered for a penicillin molecule interacting with a penicillin receptor?
What is the main difference between ab initio and semiempirical methods in computational chemistry?
What is the main difference between ab initio and semiempirical methods in computational chemistry?
In computational chemistry, what is the primary objective when calculating drug-receptor interaction energy at different positions (docking)?
In computational chemistry, what is the primary objective when calculating drug-receptor interaction energy at different positions (docking)?
What is the main purpose of molecular dynamics simulations?
What is the main purpose of molecular dynamics simulations?
How does molecular dynamics handle the movement of each atom?
How does molecular dynamics handle the movement of each atom?
Why is it important for time intervals in molecular dynamics simulations to be small?
Why is it important for time intervals in molecular dynamics simulations to be small?
What is the main focus of a posteriori analysis in drug design?
What is the main focus of a posteriori analysis in drug design?
Which technique provides fast structural information and is done in a solution?
Which technique provides fast structural information and is done in a solution?
What is the significance of expressing temperature in terms of atomic velocities in simulations?
What is the significance of expressing temperature in terms of atomic velocities in simulations?
What is the main focus of Zanamivir bound in the active site of H1N1 influenza neuraminidase?
What is the main focus of Zanamivir bound in the active site of H1N1 influenza neuraminidase?
What is the typical duration of calculations for enzyme-ligands consisting of 20-30,000 atoms?
What is the typical duration of calculations for enzyme-ligands consisting of 20-30,000 atoms?
In virtual drug screening techniques, what does chemoinformatics primarily deal with?
In virtual drug screening techniques, what does chemoinformatics primarily deal with?
What is the disadvantage of X-ray crystallography compared to NMR in drug design?
What is the disadvantage of X-ray crystallography compared to NMR in drug design?
What is a key application of computational chemistry in drug discovery?
What is a key application of computational chemistry in drug discovery?
What method does not require information about the receptor in virtual drug screening techniques?
What method does not require information about the receptor in virtual drug screening techniques?
Which technique involves fitting analogues into the binding site in silico to test binding capability?
Which technique involves fitting analogues into the binding site in silico to test binding capability?
Which process involves rational design of lead compounds based on the known structure of the receptor?
Which process involves rational design of lead compounds based on the known structure of the receptor?
'Structure-based design' commonly requires knowledge of what to design drug molecules?
'Structure-based design' commonly requires knowledge of what to design drug molecules?
What was a significant result of random screening on all available substances during the HIV discovery phase?
What was a significant result of random screening on all available substances during the HIV discovery phase?
'Ca2+ channel antagonists and K+ channel activators' are particularly important for which therapeutic area?
'Ca2+ channel antagonists and K+ channel activators' are particularly important for which therapeutic area?
'H-bonding interactions of an inhibitor of HIV-1 PR' is mainly focused on what aspect in drug discovery?
'H-bonding interactions of an inhibitor of HIV-1 PR' is mainly focused on what aspect in drug discovery?
'Drug repurposing - reprofiling - repositioning' is a strategy often used to:
'Drug repurposing - reprofiling - repositioning' is a strategy often used to:
What is the main purpose of crystalising the target protein with a bound ligand in the structure-based drug design process discussed in the text?
What is the main purpose of crystalising the target protein with a bound ligand in the structure-based drug design process discussed in the text?
In structure-based drug design, why is it essential to identify vacant regions for extra binding interactions?
In structure-based drug design, why is it essential to identify vacant regions for extra binding interactions?
What is a challenge associated with designing drugs based solely on knowledge of the target binding site?
What is a challenge associated with designing drugs based solely on knowledge of the target binding site?
Which approach is suggested for designing drugs that interact with multiple targets in drug discovery?
Which approach is suggested for designing drugs that interact with multiple targets in drug discovery?
Why is designing agents that interact with two or more targets advantageous in drug development?
Why is designing agents that interact with two or more targets advantageous in drug development?
What role does luck play in drug design according to the text's discussion?
What role does luck play in drug design according to the text's discussion?
Why might logical step-by-step modifications not always lead to improved drug activity?
Why might logical step-by-step modifications not always lead to improved drug activity?
Study Notes
Molecular Dynamics Simulations
- Used to simulate the behavior of a system
- Breaks down dynamics into movements of individual atoms
- Calculates velocities and forces acting on atoms using Newtonian equations
- Tracks atomic positions and velocities at each step
- Energy calculation is performed for each configuration using molecular mechanics
Molecular Dynamics Time Steps
- Time intervals for calculations should be small enough to simulate fastest atomic motions
- Example: C-H bond vibrations have a period of 10^-14 seconds, so time step should be around 10^-15 seconds (1 femtosecond)
Effect of Temperature
- Simulation of molecular motion can be done at high temperatures to overcome energy barriers
- Temperature is expressed in terms of atomic velocities
Typical Molecular Dynamics Studies
- Simulation of a system of up to 500,000 atoms is possible
- Typical enzyme-ligand systems consist of 20-30,000 atoms and take several weeks of computer time
- Process involves:
- Building the target protein model from X-ray or NMR results
- Adding the ligand and immersing it in a box of water or applying a dielectric constant
- Performing energy minimization to relax the initial molecule
- Heating the system to the required temperature
- Performing calculations for 250 picoseconds to 25 nanoseconds with a sampling time step of 1 femtosecond
Processing of Results
- Find the lowest-energy binding mode
- Track interatomic distances between residues of interest
- Calculate properties, such as free energy of binding
Virtual Drug Screening Techniques (Chemoinformatics)
- Deals with a massive amount of molecules for their biological behavior
- Methods include:
- Drug-receptor docking: calculating interaction energies between ligands and the protein
- Ligand-based methods: QSAR or pharmacophore-based methods
- Virtual combinatorial chemistry methods: designing a diverse set of molecules for screening
Computational Chemistry
- Required for accurate modeling of molecular behavior
- Properties should be calculated and assigned
- Theoretical model should accurately estimate or reproduce experimental results
Molecular Modelling
- Offers techniques beyond traditional graphs
- Visualizes molecular properties, such as:
- Mapping positively charged parts with red and negatively charged parts with blue
- Hydrophobicity
- Non-physical properties, such as conservation of residues or similarity to other proteins
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Description
Test your knowledge on computational methods in medicinal chemistry with this quiz based on Dr. A. Edwards' lecture 7 from MSOP1016 at Medway School of Pharmacy. The quiz covers topics like drug discovery, drug design, and the role of computers in medicinal chemistry.
