Computational Modelling of Chemical and Biochemical Reactivity

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Computational Modelling of Chemical and
Biochemical Reactivity
Ian Williams
Chemistry
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(No Transcript)
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A Chemical Landscapemountain pass º
transition state
D

C
B
E
T






Map coordinates longitude latitude Contour
lines vertical height µ potential energy
(gravitational)
W
G
R

W
4
"
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Relenza and Tamiflu stop the virus from budding
out of the cell
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quantummechanicsSchrödinger equation
neuraminidase
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Neuraminidase5668 atoms
quantummechanicsSchrödinger equation
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5668 atoms
37 atoms
quantummechanicsSchrödinger equation
Neuraminidase in water 50177 atoms
classical mechanics Hooke Coulomb
85 atoms
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Quantum mechanics Molecular mechanics
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Molecular dynamics Newtons Laws
Elaboration of series of MD simulations along an
appropriate coordinate using a biasing potential
Þ Potential of Mean ForceÞ Free energy
changescorresponding to chemical kinetics and
equilibria
T 300KQM/MM potential for 50,000 atoms within
periodic boundary conditions
A typical MD trajectory within an umbrella
sampling window takes 10 CPU days to perform 20
ps equilibration 20 ps production run to
average over the sampled configurations
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exchange/correlationfunctional

• systematic improvement of QM/MM MD simulations
  requires simultaneous advances in multiple
  dimensions, each one being computationally
  demanding

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IHW groups computing resources at Bath

• Chemistry machine room
• 30 x Pentium PCs running Linux
• 3 x dual 2.2 GHz AMD Opteron, 2 x 4 Gb 1 x 8 Gb
  memory, 2 x 80 Gb 1 x 300 Gb disk

• BUCS machine room
• Share of Skein (HEFCE JREI, May 2002)

• Pauling (BBSRC, June 2005) Linux (SUSE 9) cluster
  with
• 1 x Front-end dual 2.2 GHz AMD Opteron, 2 Gb
  memory, 1 Tb RAID 5
• 32 x (dual 2.4 GHz CPU, 4 Gb memory, 120 Gb disk)
• 4 x (dual-core dual 2.2 GHz CPU, 8 Gb memory,
  120 Gb disk)
• Gigabit interconnect

• Upgrade 2007 with EPSRC funding (awarded)
• Further BBSRC pending decision

Thank you for listening!