Automated Ligand Binding Prediction in Medicinal Chemistry

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What is the purpose of AutoSite in medicinal chemistry?

To screen compounds for potential toxicity

To analyze the structure of biological molecules

To predict automated ligand binding (correct)

To design new pharmaceutical drugs

Which of the following methods is used to find ligands or fragments by docking?

High-Throughput Screening (HTS)

Solvation Energy for Exhaustive Docking (SEED)

rDock

All of the above (correct)

What is the importance of Hill slopes in High-Throughput Screening (HTS)?

To screen out PAINS compounds

To analyze the structure of biological molecules

To determine the binding affinity of compounds (correct)

To identify potential toxicity of compounds

What is the purpose of avoiding PAINS compounds in medicinal chemistry?

To prevent interference with assay results Signup and view all the answers

What is the difference between Virtual Screening and High-Throughput Screening (HTS)?

Virtual Screening is used for in silico screening, while HTS is used for in vitro screening Signup and view all the answers

What is the main advantage of using docking methods in medicinal chemistry?

They can predict the binding affinity of compounds Signup and view all the answers

What is the function of the channel lined with hydrophobic residues in the COX-1 active site?

It provides a pathway for the substrate to access the active site from the interior of the membrane Signup and view all the answers

What is the function of Arg120 in the COX active site of PGHS-1?

Binds to the carboxylate group of fatty acid substrates Signup and view all the answers

What is the result of the oxidation of the heme group by ROOH in the POX site?

Activation of the COX activity Signup and view all the answers

What is the role of Tyr 385 in the COX catalytic mechanism?

It interacts with the carboxyl group of the arachadonic acid substrate Signup and view all the answers

What is the main function of prostaglandin-H2 synthase (COX) in the body?

To convert arachidonic acid to prostaglandin H2 Signup and view all the answers

What is the result of the cyclization reaction in the COX catalytic mechanism?

The formation of a hydroperoxide Signup and view all the answers

What is the difference between the cyclooxygenase and peroxidase activities of COX?

Peroxidase activity involves the heme group, while cyclooxygenase activity occurs at a separate active site Signup and view all the answers

What is the function of the tyrosyl radical in the COX cycle?

Abstracts the 13proS hydrogen from AA Signup and view all the answers

What is the outcome of the two sequential one-electron reductions of Compound I?

Formation of the resting enzyme plus H2O Signup and view all the answers

What is the rate-limiting step in the COX reaction?

The abstraction of the 13-proS hydrogen atom from arachadonic acid Signup and view all the answers

What is the main difference between COX1 and COX2?

COX1 is constitutively expressed, while COX2 is inducibly expressed Signup and view all the answers

Where does aspirin bind to inhibit COX activity?

COX site Signup and view all the answers

What is the function of the peroxidase (POX) site in PGHSs?

It acts as a peroxide substrate to regenerate the heme Compound I Signup and view all the answers

What is the function of COX1 in the body?

To protect the gastric mucosa and regulate kidney function Signup and view all the answers

How many amphipathic helices from each monomer are involved in COX-1 membrane binding?

Four Signup and view all the answers

What is the structural organization of COX1?

A dimeric protein with separate active sites for cyclooxygenase and peroxidase activities Signup and view all the answers

What is the significance of Ser530 in the COX cycle?

It is the site of acetylation by aspirin Signup and view all the answers

What is the role of COX2 in the body?

To respond to inflammation Signup and view all the answers

What is the effect of aspirin on platelet COX1?

It reduces thromboxane production Signup and view all the answers

What is the estimated sales of Celebrex in 2004?

$3.3 billion Signup and view all the answers

What is the role of COX2 in vascular endothelial cells?

It inhibits platelet aggregation and promotes vasodilation Signup and view all the answers

What is the name of the FDA-approved drug developed by Searle and marketed by Pfizer?

Celebrex Signup and view all the answers

What is the consequence of altering the thromboxane:prostacyclin ratio in cardiovascular health?

It leads to myocardial infarction and death Signup and view all the answers

What is the substrate for COX enzymes?

Arachidonic Acid (AA) and other fatty acids Signup and view all the answers