nucleic lec 12

<p>They allow for rapid testing of multiple compounds against targets. (D)</p> Signup and view all the answers

<p>Recruiting a sufficiently diverse and representative patient population. (A)</p> Signup and view all the answers

<p>80 - 90% (D)</p> Signup and view all the answers

<p>Its structure (A)</p> Signup and view all the answers

<p>Lead optimization (B)</p> Signup and view all the answers

<p>&lt; 1 µl (A)</p> Signup and view all the answers

<p>Non-specific interactions (D)</p> Signup and view all the answers

<p>Affinity and selectivity (B)</p> Signup and view all the answers

<p>$2 billion and 15 years (B)</p> Signup and view all the answers

<p>Finding compounds that bind to a target (D)</p> Signup and view all the answers

<p>Conduct in vitro and animal trials for safety (C)</p> Signup and view all the answers

<p>Enhancing drug affinity and specificity (C)</p> Signup and view all the answers

<p>To evaluate safety and efficacy in laboratory settings (B)</p> Signup and view all the answers

<p>Prove safety and efficacy in human subjects (A)</p> Signup and view all the answers

<p>It must have been approved by a government body (A)</p> Signup and view all the answers

<p>Careful evaluation of potential adverse effects (B)</p> Signup and view all the answers

<p>Obtaining an adequate number of suitable volunteers (D)</p> Signup and view all the answers

<p>Market viability (A)</p> Signup and view all the answers

<p>High molecular weight for increased stability (D)</p> Signup and view all the answers

<p>It minimizes resource requirements for drug projects (B)</p> Signup and view all the answers

<p>33% (A)</p> Signup and view all the answers

<p>Tight binding to target (D)</p> Signup and view all the answers

<p>To maintain efficacy at low concentrations (B)</p> Signup and view all the answers

<p>AlphaFold 2 models (A)</p> Signup and view all the answers

<p>High lipophilicity (D)</p> Signup and view all the answers

<p>They enable virtual screening of drug-like molecules. (D)</p> Signup and view all the answers

<p>It can enhance virtual screening and affinity optimization. (C)</p> Signup and view all the answers

<p>It identifies unexploited interactions for binding energy. (C)</p> Signup and view all the answers

<p>They allow for real-time adjustments during clinical trials. (B)</p> Signup and view all the answers

<p>The cost associated with physical drug trials. (B)</p> Signup and view all the answers

<p>Improving the likelihood of effective drug-target interactions. (B)</p> Signup and view all the answers

<p>It provides a framework for pre-screening compounds. (A)</p> Signup and view all the answers

<p>Inhibiting the synthesis of prostaglandins (B)</p> Signup and view all the answers

<p>Cyclooxygenase 2 (COX-2) (B)</p> Signup and view all the answers

<p>Formation of a covalent bond (D)</p> Signup and view all the answers

<p>Creation of highly addictive drugs (A)</p> Signup and view all the answers

<p>It binds to the same pocket as Aspirin but does not acetylate (C)</p> Signup and view all the answers

<p>It synthesizes prostaglandins. (A)</p> Signup and view all the answers

<p>By acetylating the side chain of Ser530. (B)</p> Signup and view all the answers

<p>Absorption (A)</p> Signup and view all the answers

<p>The breakdown of the compound by the liver (B)</p> Signup and view all the answers

<p>To avoid designing inherent problems into the compound (A)</p> Signup and view all the answers

<p>The adverse side effects caused by the drug (D)</p> Signup and view all the answers

<p>Detection (D)</p> Signup and view all the answers

<p>X-ray Crystallography (C)</p> Signup and view all the answers

<p>It can detect very weakly binding ligands. (A)</p> Signup and view all the answers

<p>It shows how multiple fragments can interact with each other. (A)</p> Signup and view all the answers

<p>Knowledge of fragment co-structures. (C)</p> Signup and view all the answers

<p>Binding energies are additive. (B)</p> Signup and view all the answers

<p>Surface Plasmon Resonance (D), Native mass spec (A)</p> Signup and view all the answers

<p>It reveals how ligands bind and coordinate their interactions. (B)</p> Signup and view all the answers

<p>mM (B)</p> Signup and view all the answers

<p>Native Mass Spectrometry = ✔️ Detects Binding NMR = ✔️ Reveals Binding Site X-ray Crystallography = ✔️ Shows Binding Mode Surface Plasmon Resonance = ✔️ Reveals Affinity</p> Signup and view all the answers

<p>Native Mass Spectrometry = Binding Only NMR = Binding and Site X-ray Crystallography = Binding, Site, and Mode Surface Plasmon Resonance = Binding Only</p> Signup and view all the answers

The process of creating new drug compounds, testing their activity, selectivity, toxicity, and other properties.

Drugs must bind strongly to their targets (low nanomolar range) for effectiveness at low concentrations.

Drugs need to be soluble to be absorbed and distributed in the body.

Drugs must be lipophilic enough to dissolve in cell membranes to enter and exit cells.

A drug discovery method that screens building blocks of a large library, prioritizing related hits.

Computer models used in drug discovery to predict protein structures, used for docking purposes.

Protein models in a single structural state used in computations in drug discovery.

Tests that assess how well a drug molecule fits into the target protein structure.

A measure of how tightly a drug binds to its target.

Drug compounds that are strong candidates for clinical use.

Developing and approving a new drug typically takes about 15 years and costs around US$2 billion.

Choosing a specific molecular target (often a protein) to focus on in order to efficiently create the desired biological effect.

An initial screening method used in drug discovery to identify compounds that bind to the target protein from a vast library of synthesized compounds.

Compounds that show a positive result in the initial screening tests, but may not have the desired biological effect.

Compounds identified from "hits" that exhibit a desirable biochemical effect and are suitable for further optimization and investigation.

The process of modifying a "lead" compound to improve its desired properties, such as binding affinity, selectivity, and toxicity profile.

A specific molecule (usually a protein) that a drug or other molecule interacts with to create a desired effect.

A test that measures a specific biochemical reaction or process to determine if a compound interacts with the target.

Using cryo-electron microscopy (CryoEM) to identify structural states of proteins, potentially leading to screening for proteins without known structures.

Advanced AI model that predicts protein-drug complexes with high accuracy (up to 93% within 2 Å RMSD).

Computational method to screen drug-like molecules without expensive high-throughput screening (HTS).

Computational method to identify potential drug candidates based on target protein structure.

Computational technique to modify existing compounds for improved binding to target proteins.

Unintended side effects of a drug on different parts of the body or components of the body.

Root Mean Square Deviation, a measure of difference between two structures used to gauge accuracy of a prediction.

Structures formed when a drug molecule binds to a protein.

Using computers to find potential drug candidates without lab trials.

A multi-stage process to develop new medicines, starting with identifying a disease target and ending with regulatory approval.

A molecule with potential to treat a disease

Governmental process to ensure safety and efficacy of new drugs before sale

Testing new drugs on lab-models and animals before human trials;

Testing a drug on volunteers and patients to assess safety and efficacy

Absorption, Distribution, Metabolism, Excretion, and Toxicity of a compound

Developing drugs based on understanding the disease's processes

Finding drug candidates through a methodical approach

Ensuring a drug has minimal or acceptable side effects in humans

A drug is a chemical entity that produces a desired therapeutic effect. It can be a small molecule (like penicillin or viagra) or a protein (like insulin).

Most drugs work by specifically binding to and affecting a biological target, usually a protein. This binding interaction causes a specific change in the target's function.

A target is a specific molecule in the body that a drug interacts with. Most targets are proteins, but other molecules like DNA or RNA can be targets too.

Specificity is important because drugs should only affect their intended target, minimizing side effects. A drug that interacts with multiple targets might cause unwanted effects.

Aspirin (acetyl salicylic acid) was the first synthetic drug. It was discovered when scientists modified salicylic acid to reduce side effects.

Aspirin works by inhibiting the enzyme COX-2, which prevents the production of prostaglandins, molecules involved in inflammation and pain.

COX-2 is an enzyme that produces prostaglandins, which are involved in inflammation and pain.

Prostaglandins are molecules involved in various bodily processes, including inflammation and pain. COX-2 produces them.

Aspirin irreversibly inhibits COX-2 by attaching an acetyl group to a specific amino acid (Ser530) in the enzyme.

Heroin was initially marketed as a safer alternative to morphine because it was believed to be less addictive.

Drugs need to bind strongly to their target for effectiveness, be soluble for absorption, and lipophilic to cross cell membranes.

Drugs need to be soluble enough to be absorbed in the gut, but also lipophilic to cross cell membranes.

Acetylation is important because it allows aspirin to irreversibly bind to COX-2, making it a much more effective pain reliever than salicylic acid, which only weakly binds.

Drugs need to be soluble in the gut to be absorbed, but they also need to be lipophilic enough to cross cell membranes. It's a balancing act between solubility and lipophilicity.

The ability of a drug to enter the body, usually through the gastrointestinal tract (GI) or intravenously.

The process of a drug moving throughout the body and reaching different tissues and organs.

The breakdown of a drug by the liver and other organs.

The elimination of a drug and its byproducts from the body, often through urine or feces.

A method used in drug discovery to identify small molecules (fragments) that bind to a target protein, providing the foundation for designing larger, more potent drugs.

A technique used in fragment screening that detects weak binding of molecules to a target protein. It measures the mass of the protein and its complexes with different fragments.

Nuclear Magnetic Resonance (NMR) is used to analyze the binding of ligands (small molecules) to proteins and identify the binding site. NMR is sensitive and can detect even very weak binding.

X-ray crystallography is used to determine the 3D structure of a protein and its complex with a fragment. It reveals the binding site and how a fragment interacts with the protein.

In drug design, two fragments that bind to a target protein closely together can be linked chemically to create a single molecule with enhanced binding affinity.

The 3D structures of two or more fragments bound to the same target protein. These structures guide the design of linkers to combine fragments.

Characteristics of a molecule that make it suitable for a drug, such as small size, appropriate solubility, and good binding affinity to the target protein.

When two fragments bind separately to a target protein, the total binding energy of the linked molecule is often higher than the sum of the individual fragment binding energies.

Different techniques used to study how proteins bind to ligands, such as small molecules or drugs. Examples include X-ray crystallography, NMR, and Mass Spectrometry.

Identifying whether a protein and a ligand interact with each other.

Pinpointing the specific location on the protein where the ligand attaches.

Describing the precise way the ligand interacts with the protein, like a handshake or a hug.

Measuring how strongly the ligand binds to the protein, quantifying their attraction.