In Silico Drug Design: Molecular Modelling Techniques

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What is one advantage of having a loose-fitting structure in molecule design?

Enables fine-tuning of the structure (correct)

Leads to a rigid conformation

Prevents any binding from occurring

Allows for precise prediction of binding

In LUDI method, what is the first step involved in de novo design of ligands for proteins?

Searching libraries for fragments

Making hypothetical active sites for unknown receptor proteins

Fitting molecular fragments onto interaction sites

Calculating interaction sites within the protein's active site (correct)

Why are flexible molecules preferred over rigid molecules in molecule design?

Rigid molecules bind more effectively

Flexibility allows modification based on actual binding site (correct)

Rigid molecules have stable conformations

Flexible molecules allow for easier synthesis

What does LUDI distinguish when generating interaction sites for protein atoms or functional groups?

Lipophilic and aromatic interactions Signup and view all the answers

What does the LUDI method do if the structure of the receptor protein is unknown?

Makes hypothetical active sites based on known ligands' characteristics Signup and view all the answers

What is an essential consideration in molecule design to ensure stability?

Considering feasible synthesis routes Signup and view all the answers

What is a potential disadvantage of using more flexible molecules in conformational analysis?

They have multiple possible conformations to consider Signup and view all the answers

What is the primary purpose of overlaying molecules in structural comparison of active compounds?

To determine the common volume or space for important binding groups Signup and view all the answers

What is a limitation of computers when it comes to automatic docking of ligand to binding site?

They lack spatial awareness Signup and view all the answers

What is the significance of spheres with radii > 5 Å being rejected in DOCK program guidelines?

They are too large to fit in the binding site Signup and view all the answers

What is the main principle of de novo drug design?

Do not fill the entire space in the binding site Signup and view all the answers

What is the purpose of 3D pharmacophore identification?

To identify the common pharmacophore triangles Signup and view all the answers

What does LUDI use to search for suitable interaction sites?

Distance criteria Signup and view all the answers

How does LUDI fit the fragment?

By performing a root mean square (RMS) superposition Signup and view all the answers

What does LUDI imply in terms of positioning a fragment?

It positions the fragment to take advantage of nearby interaction sites Signup and view all the answers

How are link sites defined on the ligand?

Link sites are defined by hydrogen atoms Signup and view all the answers

What method does LUDI use to simultaneously align the fragment to a ligand link site?

LUDI does not actually create the ligand-fragment bond(s). It implies positions the fragment in such a way as to take advantage of nearby interaction sites. Signup and view all the answers

What is the purpose of compound libraries?

To create many compounds rapidly using combinatorial and parallel synthesis Signup and view all the answers

What is the primary benefit of starting with a rigid structure in pharmacophore searching?

It increases the likelihood that most conformations will be represented during interaction with the target. Signup and view all the answers

Why is it important to measure activity against a range of targets in drug development?

To ensure that the compounds show selectivity. Signup and view all the answers

How does starting with the most rigid structure in pharmacophore searching reduce the number of required synthetic products?

By reducing the number of possible conformations during interaction with the target. Signup and view all the answers

What is the advantage of using molecular modelling in pharmacophore searching?

It reduces the number of required synthetic products. Signup and view all the answers

What is the primary factor considered when ranking synthetic products based on rigidity?

The number of rotatable bonds. Signup and view all the answers

What is the primary reason for rejecting associated pharmacophores during comparison in pharmacophore searching?

If the second set of pharmacophores is >10% different from the first set. Signup and view all the answers

Which approach explicitly models the electrons of each atom?

Quantum Mechanics Signup and view all the answers

Which method is best suited for molecules containing 1000's of atoms?

Molecular Mechanics Signup and view all the answers

Which property can be predicted using ChemDraw Ultra?

Theoretical elemental analysis Signup and view all the answers

Which representation is used to identify areas of a molecule that are electron rich or poor?

Molecular electrostatic potentials Signup and view all the answers

How can the best conformations with the lowest energy be found using molecular dynamics?

By simulating heating to allow bond stretching and rotation Signup and view all the answers

Which method is the most accurate but computationally intensive?

Ab Initio Signup and view all the answers

Which method is used to compute the electrostatic interaction energy in molecular mechanics force fields?

Partial charges Signup and view all the answers

What does the RMSD value indicate in a 2D overlay of two molecules?

The best fit of the functional groups in the two molecules Signup and view all the answers

Which method is used to determine the potential energy of an atom in molecular dynamics?

Non-bonding interactions with neighbouring molecules Signup and view all the answers

Which technique is used to study molecular motion?

Molecular Dynamics Signup and view all the answers