Module 2: MD

Question 1

Pair Potentials

Answer 1

• O(N²) → O(N )
• to parameterize, compare to experimental or post-HF results
  
  • dihedral parameters must be fit to post-HF results
  • can coarse-grain parameterization beyond elemental atoms (e.g. DNA base-pairs)

Question 2

Explicit Water Models

Answer 2

• there exist different parameterizations of water mocules
  
  • e.g. SPC, SPC/E, TIP4P, etc
• no size fits all
  
  • each parameterized to reproduce specific quanities in specific scenarios
• some models are force field specific

Question 3

SPC/E Model

Answer 3

• extends simple point charge model by modifying partial charge on oxygen and adding constant polarization energy
  
  • better density and diffusion

Question 4

Polymers

Answer 4

• coarse-grain polymers with force-fields for interactions
• usually investigate
  
  • diffusion
  • thermodynamic properties
  • radius of gyration
  • end-to-end distance

Question 5

Radius of Gyration

Answer 5

• measure of polymer extension
• scales with number of monomers to the Flory exponent
  
  • can measure scaling of radius of gyration in specific solvent to determine solvent type

Question 6

Flory Exponent and Solvent Types

Answer 6

νSolvent

1 Coulomb repulsion only

0.63 good

1/2 θ

1/3 poor

Question 7

θ-Solvent

Answer 7

• implicit solvent
• ideal chain polymer
  
  • nearest-neighbor harmonic interaction only

Question 8

Good Solvent

Answer 8

• excluded volume interactions
  
  • WCA potential
• FENE model
  
  • finitely extensible non-linear elastic model

Question 9

Poor Solvent

Answer 9

LJ interaction only

Question 10

Osmolytes

Answer 10

cosolvents, like osmolyts, can affect the solvent as well as the solute

• Solvent Effects:
  
  • kosmotropes: order making; causes water molecules to favorably interact, effectively stabilizing intramolecular interactions in macomolecules
  • chaotropes: disorder making; disrupts hydrogen bond network in water, which weakens hydrophic effect in macromolecules
• Solute Effects:
  
  • denaturant: causes folding of protein to be altered such that it becomes biologically inactive

Question 11

Simulation Methods Overview

Answer 11

• investigated water dyanmics around anti-freeze protein and urea/hydroectoine cosolutes to determine if osmolytes are kosmo-/chaotropes
  
  • preferential binding
  • activity coefficient
  • hydrogen bond lifetimes
  • dipole relaxation time

NOTE: Protein found in animals that can survive in water around freezing point of their own blood

Question 12

Preferential Binding

Answer 12

• thermodynamic expression that describes the binding of the cosolcent over the solvent
• allows identification of solutes that participate in a reaction
• measured through Kirkwood-Buff Theory
  
  • 1 ≡ primary colvent
  • 2 ≡ solute
  • 3 ≡ cosolvent

Question 13

Activity Coefficient

Answer 13

• used to account for deviations from ideal behavior in a mixture of chemical substances
  
  • ideal ≡ microscopic interactions between each pair of chemical species are the same; macrosopic enhatlpy change of solution and volume variation in mixing is zero
• a_ii < 0 → suggests chaotropic behavior

Question 14

(Forward) Hydrogen Bond Lifetime

Answer 14

• gives insight into how “structured” hydrogen bond network of water is
• C_HB ≡ existence criteria auto-correlation function
  
  • specificy distance and angle that constitutes “bond”

Question 15

Average Water-Dipole Relaxation Time

Answer 15

• measure of time it takes for orientation polarization of a substance to teach equilibrium
  
  • Hight T_w → increases electrostatic interactions → preserves protein structure

Question 16

Kirkwood-Buff Theory

Answer 16

• derives thermodynamic quantities from pair correlation functions between all molecules in a multicomponent system
• RDF normalized to density of component j in bulk

Question 17

KB Integral

Answer 17

• assuming spherical symmetry
• quantifies excess/deficiency of particle j around particle i
• Computational Process
  
  • post-production processing
  • ensure RDF → 1 for larger r
    
    • may fluctuate around 1 → normalize at this point
  • numerically integrate G_ij