Biomolecular Modelling

Vakinformatie

Dit vak wordt gegeven door Prof. Arnout Voet. Er zijn enkele dingen veranderd in 2022 vergeleken met de ECTS fiche. Doorheen het semester zijn er enkele verplichte sessies waarbij je de basis leert van werken in UNIX en een molecular dynamics simulation uitvoert, voor aanwezigheid krijg je dan ook punten (ik dacht 1 of 2 op 20, niet zeker). Je moet ook een taak indienen (5/20 punten) waaraan gewerkt wordt tijdens de lessen.

ECTS-fiche: https://onderwijsaanbod.kuleuven.be/syllabi/e/G0G79AE.htm

Examenvragen

Exam of 15/01/2024

1. (Oral question) You have the structure of a receptor and a few active ligands that inhibit a receptor. There is no structure of the complex. The ligands inhibit the receptor but can not be used as drug. There is a database of drug-like compounds which you need to computationally scan to find active ligands. Which methods could you use and how do they work? (15)

2. 15 multiple choice questions about the entire course. There was one question for each of the papers. (15)

3. The main differences and similarities between genetic algorithms and monte carlo simulated annealing. (10)

Exam of 16/01/2023 (This exam was written instead of oral, due to the Covid-19 restrictions. One open question was replaced by multiple choice questions.)

1. 15 multiple choice questions about the entire course. There was one question for each of the papers. (15)

2. You have the structure of a receptor and a few active ligands that inhibit a receptor. There is no structure of the complex. The ligands inhibit the receptor but can not be used as drug. There is a database of drug-like compounds which you need to computationally scan to find active ligands. Which methods could you use and how do they work? (10)

3. The main differences and similarities between genetic algorithms and monte carlo simulated annealing. (7)

4. True or false questions (8):

a. The PDB file format the best for proteins and small molecules (drugs) (2)
b. A small molecule FF can be used for proteins.(2)
c. The first step in the conjugated gradient method is the same as in the steepest descent. (2)
d. The goal of the lead optimization phase is to increase the potency of the molecule. (2)

Exam of 17/01/2022 (This exam was written instead of oral, due to the Covid-19 restrictions)

1. Describe the different methods for structure prediction and explain in which situation they are used. (15)

2. Question about the paper : Explain how (at which stages) molecular dynamics simulations were used during the creation of the signalosome by the group of DE Shaw (5)

3. You have the structure of a receptor and a few active ligands that inhibit a receptor. There is no structure of the complex. The ligands inhibit the receptor but can not be used as drug. There is a database of drug-like compounds which you need to computationally scan to find active ligands. Which methods could you use and how do they work? (10)

4. The main differences and similarities between genetic algorithms and monte carlo simulated annealing. (8)

5. True or false questions:

a. The PDB file format the best for proteins and small molecules (drugs) (3)
b. A small molecule FF can be used for proteins.(3)
c. The first step in the conjugated gradient method is the same as in the steepest descent. (3)
d. The goal of the lead optimization phase is to increase the potency of the molecule. (3)

Exam of 09/01/2021 (This exam was written instead of oral, due to the Covid-19 restrictions)

1. What is the concept of Monte Carlo Simulated Annealing? Which applications of this for biomolecular modelling have we seen in this course? (10)

2. PDB file given as an image. What do each of the columns represent? How has this data been obtained? (X-ray or NMR) (4) - this image was missing on the exams so the question got removed, bringing the total of the exam from 50 to 46

3. What is a scoring function? What are they used for, and which kinds exist? (10)

4. You have a set of active ligands that inhibit a receptor, but they can not be used as drug, and the structure of the receptor is not known. There is a database of drug-like compounds which you need to computationally scan to find active ligands. Which methods could you use and how do they work? (8)

5. True or false questions:

a. All FF should have a term for hydrogen bonds. (2)
b. Molecular dynamics is the best method to predict the structure of a protein. (2)
c. The first step in the conjugated gradient method is the same as in the steepest descent. (2)
d. The goal of the lead optimization phase is to increase the potency of the molecule. (2)

  Two questions based on research articles (10)
a. What is BEDROC used for, and how does it differ from ROC?
b. You want to model a small protein that inhibits the protein-protein interaction of two larger proteins. There are two ways to do this discussed in the article, which one would you choose? Explain.

Exam of 21/01/2020

1. Describe the different methods for structure prediction and explain in which situation they are used.

2. Differences and similarities between genetic algorithms and monte carlo simulated annealing.

3. You have a set of molecules able to bind a target, but they can not be used as drugs. There is a database of drug-like compounds. You have the structure of the active ligands, of the target but not of the complex. What would you do to find new drugs

4. Random question: describe the steps of molecular dynamics

5. True or false questions:

       a. The PDB is the best format to store data of protein-ligand complexes 
       b. FF for small molecules can not be used for proteins
       c. The first step of conjugate gradient is steepest descent

Exam of 20/01/2020

1. (Oral) Describe Monte Carlo simulation and what it is used for.

2. (Oral)Random question, possible questions are:

1. explain the enrichment factor.
2. describe the set-up of a MD simulation

3. What is a scoring function and which types are there?

4. You have a set of molecules able to bind a target, but they can not be used as drugs. There is a database of drug-like compounds. You have the structure of the active ligands, of the target but not of the complex. What would you do to find new drugs

5. 4 true or false questions:

      a. All FF should have a term for hydrogen bonds.
      b. Molecular dynamics is the best method to predict the structure of a protein.
      c. The first step in the conjugated gradient method is the same as in the steepest descent.
      d. The goal of the lead optimization phase is to increase the potency of the molecule.