Molecular Dynamics and Molecular Modeling CHEM 388

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Molecular Modeling, Simulation and Design
Principles and Applications
CHEM 388
http//sdixit.web.wesleyan.edu/wescourses/2006s/ch
em388/01/mdcourse/

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Specific Aims

• Essential computer skills
• Fundamentals of Modeling, Simulation and related
  procedures The Chemical Physics
  
• Applications of Molecular Dynamics Simulation and
  related procedures The Molecular Biophysics
  
• Analysis
• Electrostatics, Free energy calculations
• Docking
• Cheminformatics

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Types of Molecular Models

• Conceptual
• Mathematical
• Experimental
• X ray, NMR
• Computational
• Deterministic (MD)
• Probabilistic (MC)

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Classification of Molecular Systems and
Simulations
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Choice of Molecular Model
Process of Interest
Modeling Technique Force Field, Solvent, Sampli
ng
Required Accuracy
Size / Computing Power
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Growth in Structural Data

• 120 to 280 therapeutic proteins, but less than 5
  has been developed!
  
• 5000 to 10 000 novel drug targets are there but
  currently research is based on 500 drug targets!

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Molecules in motion!
HIV protease inhibitor Ritonavir binding to the
protease http//www.umass.edu/microbio/chime/exp
lorer
Information flow through membrane receptors
http//bio.winona.msus.edu/berg/ANIMTNS/Recep.htm
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Vision of Newtonian Mechanics
An intelligence which could, at any moment,
comprehend all the forces by which nature is
animated and the respective positions of the
beings of which it is composed, and moreover, if
this intelligence were far-reaching enough to
subject these data to analysis, it would
encompass in that formula both the movements of
the largest bodies in the universe and those of
the lightest atom to it nothing would be
uncertain, and the future, as well as the past,
would be present to its eyes. The human mind
offers us, in the perfection which it has given
to astronomy, a faint sketch of this
intelligence. -Laplace in Oeuvre 1820
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Time Scales of Biological Motions
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Simulation of a Box of Argon Particles
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Molecular Dynamics Trajectory of CAP-DNA Complex
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Choice of Molecular Model
Process of Interest
Modeling Technique Force Field, Solvent, Sampli
ng
Required Accuracy
Size / Computing Power
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Evolution of Computing Power
1977 BPTI, vacuum 0.01 ns
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1983 DNA, vacuum 0.09 ns
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1992 HIV Protease, water 0.11 ns
4
1998 DNA, water 14 ns
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1998 Villin headpiece, water 1000 ns
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2002 channel protein in membrane 5 ns
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2004 DNA 25000 atoms, 0.6 ms
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Source Moravac, Robots, Oxford 1999
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The Basic Computer Hardware
Motherboard
Processor
Hard Disk/Storage
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Parallel Processing

• Why ? Limitations Memory, Time
• How ?

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Pittsburgh Supercomputing Center

• SCALE
• 3000 processors
• SIZE
• 1 basketball court
• COMPUTING POWER
• 6 TeraFlops (6 trillion floating point
  operations per second)
  
• Will do in 3 hours what a PC will do in a year

The Terascale Computing System (TCS) at the
Pittsburgh Supercomputing Center
Upon entering production in October 2001, the TCS
was the most powerful computer in the world for
unclassified research
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Pittsburgh Supercomputing Center

• HEAT GENERATED
• 2.5 million BTUs
• (169 lbs of coal per hour)
• AIR CONDITIONING
• 900 gallons of water per minute
• (375 room air conditioners)
• BOOT TIME
• 3 hours

The Terascale Computing System (TCS) at the
Pittsburgh Supercomputing Center
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NCSA National Center for Super-computing
Applications

• SCALE
• 1774 processors
• ARCHITECHTURE
• Intel Itanium2
• COMPUTING POWER
• 10 TeraFlops

The TeraGrid cluster at NCSA
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TACCTexas Advanced Computing Center

• SCALE
• 1024 processors
• ARCHITECHTURE
• Intel Xeon
• COMPUTING POWER
• 6 TeraFlops

LoneStar at TACC
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(No Transcript)
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The worlds largest collection of supercomputers
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Teragrid Resource Scale

• 40 teraflops (1012) compute
• Desktop CPU 2GHz
• 1 petabyte (1015) online storage
• Desktop Machine hard Disk Storage 80GB
• 10-40Gbps networking
• Modem a few Kbps
• LAN a few Mbps

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TeraGrid Resources
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Before the TeraGridSupercomputing The Old
Fashioned way

• Each supercomputer center was its own
  independent entity.
  
• Users applied for time at a specific
  supercomputer center
  
• Each center supplied its own
• compute resources
• archival resources
• accounting
• user support

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The TeraGrid Strategy

• Creating a unified user environment
• Single user support resources.
• Single authentication point
• Common software functionality
• Common job management infrastructure
• Globally-accessible data storage
• across heterogeneous resources
• 7 computing architectures
• 5 visualization resources
• diverse storage technologies

• Create a unified national HPC infrastructure that
  is both heterogeneous and extensible