A COMPARATIVE MOLECULAR DYNAMICS STUDY OF THE EFFECT

OF ALPHA-TOCOPHEROL AND CHOLESTEROL ON PHOSPHOLIPID

BILAYERS HAVING DIFFERENT LEVELS OF ACYL CHAIN

UNSATURATION

James GormanWabash College

Background

Phospholipid:• class of lipid• usually contains a phosphate group• hydrophilic head• hydrophobic tail

Bilayer:• Thin membrane made of 2 layers of lipids

Membrane:• barrier between the interior and exterior• nearly all cells have a membrane• cell membranes have hydrophobic interior and hydrophilic interior

Alpha-Tocopherol (ATOC)

13 Carbon tail

Positive Health benefits:Alzheimer’s DiseaseCancerCataractsHeart Disease

Cholesterol (CHOL)

6 Carbon tail

Health Risks:Cardiovascular DiseaseHeart AttackStrokePeripheral Disease

C27H46O

SolutesC29H50O2

DPPC SDPC1,2-Dipalmitoyl-sn-glycero-3-phosphocholine

Both 16:063.1 ± 2.2 Å2/molecule

1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine

18:0 and 22:668.2 ± 1.3 Å2/molecule

Lipids

Solute EffectsDPPC SDPC

Average Lipid Area 63.1 ± 2.3 68.2 ± 1.3

Apparent CHOL area ‐1.76 ± 0.14 ‐4.05 ± 0.32

Apparent ATOC area 24.1 ± 1.9 25.7 ± 2.1

2300

2500

2700

2900

3100

3300

3500

3700

10 20 30 40 50 60 70 80 90 100 110

Are

a (Å

2 )

Time (ns)

Total Simulation Area vs. Time

atoc_sdpcchol_sdpcatoc_dppcchol_dppcpure_sdpcpure_dppcpure_dppcpure_dppcpure_dppc

Solute Distribution

• Atoc stays closer to center of the bilayer

• Chol remains slightly farther away from center

• Water mainly stays away from the membrane

Radial Distribution Functions

Atoc/SDPC

Atoc/DPPC

Chol/SDPC

Chol/DPPC

Radial Distribution Functions

• Have similar distributions• All spend most time near water• Hydrogen bonding

Interaction Energy

ATOC CHOL

Order Parameters

• Determine the disorder of a system• Range from 0 to 1• 0 signifies a disordered system• 1 specifies an ordered system

Θ = angle C‐H vector makes with the z‐axis

Scd=<(3/2) Cos2 (Θ)-1/2>

Solute Effects

Acknowledgements

Dr. Scott FellerMatt RoarkLucas Evans

NSF