Atomistic vs. Coarse Grained Simulations

1
Atomistic vs. Coarse Grained Simulations
all atoms vs. four-to-one mapping long
range vs. short range interactions only
quantitative vs. semi-quantitative slow
(ns) vs. fast (ms)
1 coarse grained water 4 atomistic
water

atomistic coarse
grained
2
Aggregation into a DPPC bilayer coarse grained
model
composition 1600 DPPC 250000 H2O
5 ns
0 ns
1 ns
cell size 20x20x20 nm
simulation time 250 ns
15 ns
50 ns
100 ns
180 ns
250 ns
150 ns
3
Aggregation of DPPC into vesicles
composition 1600 DPPC 1000000 H2O
simulation time 100 ns
cell size 30x30x30 nm
Surrounding water
starting structure (t0 ns)
4
0 ns random
5 ns worms
10 ns bicelle
20 ns bicelle
60 ns cup
80 ns vesicle
5
LAMELLAR
STALK
HEMIFUSION
FUSION PORE
RHOMBIC
HEXAGONAL
CUBIC
6
Lamellar to Hexagonal Transition for DOPE at low
hydration in agreement with experiment (Rand
etal)
t 0ns t 20
ns t 100 ns T280 -gt 320K
stalk formation hexagonal
phase
7
t 20 ns
t 100 ns stalk
formation hexagonal
phase
8
Folding Transition States in Proteins
In collaboration with the group of Chris Dobson
in Cambridge we have looked at transition states
in the folding of SH3 domains.
Objective To evaluate the folding propensity of
proposed transition states (TS) of the a-spectrin
SH3 domain using molecular dynamics (MD)
simulations with an explicit representation of
the solvent.
Some of the proposed transition states fold other
do not.
9
Examples showing the native state, a proposed
transition state and results of 2 independent
folding simulations.
Configuration 2
Native
Init
Folding unsuccessful
run 1
run 2
Configuration 4
Configuration 3
Folding successful
10

• Status of our contribution
• Trajectories of the simulations mentioned above
  can be made available on request
• While we have not appointed anyone specifically
  on the project we are in the
• process of advertising.
• Our aim is to specifically appoint a person
  focusing on code development who
• could interact with those groups involved in
  methods development and exploit
• our preexisting simulations..