Lecture 10 DA

Question 1

How are proteins treated in molecular dynamics?

Answer 1

As classical, physical objects.

Question 2

What does molecular dynamics define of a protein?

Answer 2

Defines how it moves, and how it interacts with other molecules.

Question 3

What assumptions are made in molecular dynamics?

Answer 3

Atoms behave like macroscopic balls.
Atoms linked by springs.
Atoms attract/repel others similar to magnets, but not quite.

Question 4

What equation is used to calculate all forces acting on an atom?

Answer 4

F=ma

Question 5

What is necessary to model a protein using molecular dynamics? What can be said about this requirement?

Answer 5

Protein structure. Highlights the limitation of this method.

Question 6

What doesan energy function describe? Is it accurate?

Answer 6

Describes all the interaction energies of all atoms in the system. Always an approximation.

Question 7

What is the energy model? What are its two components?

Answer 7

Bond angles and lengths are almost always the same.
Components:
-Covalent terms.
-Non-covalent terms.

Question 8

Describe the two components of the energy model.

Answer 8

• Covalent terms - bond distances, angles, and dihedral angles.
• Non-covalent terms - forces at distance between all non-bonded atoms.

Question 9

Name 4 types of energy involved in molecular dynamics.

Answer 9

Bond stretching energy.
Bending energy.
Torsion energy.
Non-bonded energy.

Question 10

What does the bond stretching energy indicate at high temperatures? What limitation does this impose?

Answer 10

Indicates at higher temperatures, the bond keeps stretching, and never breaks, just requiring more and more energy.
Therefore, only suitable for physiological temperatures.

Question 11

Describe bending energy.

Answer 11

Acts like a stress grip.
If an angle is made to be more obtuse or steep, will resist it, and act as a restoring energy to return it to normal configuration by countering it.

Question 12

Describe torsion energy.

Answer 12

Energy required by the phi and psi angle mobility.

Question 13

Describe non-bonded energy. What forces does it simulate?

Answer 13

Energy of attracting and repelling forces between atoms.

Simulates Van der Waals, electrostatic etc

Question 14

What is a forcefield?

Answer 14

An energy function used in simulations, made by research groups.

Question 15

What is the difference between two given forcefields?

Answer 15

They have similar maths functions, but different parameters.

Question 16

In which environment are proteins best simulated in? What environment are they typically simulated in with molecular dynamics?

Answer 16

A water environment. Molecular dynamics usually simulates them in a vacuum.

Question 17

Why is simulating proteins in a water environment so difficult?

Answer 17

There are too many water molecules in a mol to simulate it effectively.

Question 18

Describe a solution to the problem of simulating a water environment, and a limitation.
Is it the same as a full water environment, and why?

Answer 18

Involves only simulating a water ‘shell’ around the protein, of a few million molecules.
Not exactly a water environment, more a protein in a tiny droplet. Strange water tension effects at the surface are seen.

Question 19

Name and describe two approaches to dealing with simulating a water environment (aside from the workaraound).

Answer 19

Implicit - ignore the water, instead changing parameters of the protein to mimic presence of water. Not perfect.
Explicit - Periodic boundary condition created around the protein. If the boundary is crossed by a molecule, it disappears, and reappears on the other side.

Question 20

Do either implicit or explicit approaches to water simulation resolve the problem of water surface tension at the surface?

Answer 20

Implicit - no

Explicit - yes

Question 21

What is a limitation of the explicit approach to water environment simulation? Is this necessarily a problem? Explain.

Answer 21

If the cell is too small, the protein could interact with itself - self interaction. Cell must be big enough to avoid this, but more computationally expensive.
Sometimes, it is a wanted effect, ie. in a crystal.

Question 22

What is needed once mathematical forms of interaction energies are decided? Where is this obtained from (4)?

Answer 22

A set of constant parameters.
Obtained from experimental data including:
-Infra-red spectroscopy
-Bond/angle/spring constants
-X-ray diffusion structures
-QM calculations.

Question 23

What parameter are QM calculations especially useful for?

Answer 23

Torsion angles.

Question 24

Is there a consensus on what the best set of parameters are?

Answer 24

No, different forcefields use different parameters.