Computer Modeling and Visualization in Chemistry
Spring 2007
Sat 10:00am – 12:30pm
211 Havemeyer, Columbia University
Teachers:
Eric Knoll, Li Tian and Robert Abel
.
Class Format:
The 1st half of each class will consist of a lecture introducing you to the new material. The 2nd half will be
a lab section where you can perform some of the calculations and visualizations on a computer. Many of
the classes will introduce a new subject, and the course will briefly touch on a wide area of subjects in
chemistry.
Homework:
Mostly NONE!
Grading:
No letter grade, but you do need to attend the classes to receive the certificate and remain in the program.
Topics covered (tentative):
1. Structure of Molecules
Atoms, electronic structure, bonding, molecular conformations.
2. Chemical Reactions
Energies of reactions and reaction mechanisms.
3. Proteins and DNA
The Protein Data Bank, protein folding, classification of proteins, gene therapy.
4. Molecular Modeling
Molecular Mechanics, quantum mechanics, nanotechnology, supercomputers.
The above topics may be altered depending on student interest in the given or other related subjects.
1
Class Description

This survey course is for students who are interested in chemistry,
medicine, nanotechnology, computer science, or biotechnology and
who want to discover real world applications of computer technology
that go beyond typical undergraduate chemistry. The class will
touch on advanced topics such as molecular mechanics and
quantum chemistry, which are the foundations of the simulation
software packages that are now standard research tools in areas
such as organic chemistry, biochemistry and drug discovery. For
the majority of the classes, students will get hands on experience
using these software packages to visualize and study the structure
and reactivity of organic molecules, proteins and DNA.
2
Class Schedule
DATE
TEACHER
TOPIC (tentative)
1
Jan. 27
Eric
Intro to Computational Science
2
Feb.
Eric
Review of Chem. Bonding & Molecular Orbitals
3
Feb. 10
Robert
Chemical Physics
4
Feb. 17
Robert
Kinetics / Molecular Theories
5
Feb. 24
Eric
Molecular Mechanics & Quantum Mechanics
6
Mar.
Robert
Molecular Dynamics, Stat Mech, Monte Carlo
7
Mar. 10
Li
Hydrogen Bonding
3
3
Mar. 17
NO CLASS
8
Mar. 24
Robert
The Hydrophobic Effect
9
Mar. 31
Eric
Molecular Conformations / Intro to Proteins
Apr.
7
NO CLASS
10
Apr. 14
Li
Enzymes
11
Apr. 21
Eric
Bioinformatics: Diseases, NCBI
12
Apr. 28
Li
DNA / RNA
13
May.
Lin
Spectroscopy Techniques in Biochem: NMR
5
3
- Science Honors Program Computer Modeling and Visualization in Chemistry
Computational Science
Eric Knoll
4
This presentation is for educational, non-profit purposes only.
Please do not post or distribute this presentation to anyone outside
of this course.
Most of the slides in this presentation are from a course called
“Parallel Computing” taught by Prof. David Keyes at Columbia
University
5
Three “pillars” of scientific investigation



Experiment
Theory
Simulation
(“theoretical experiments”)
Computational simulation :=
“a means of scientific discovery
that employs a computer system to
simulate a physical system according
to laws derived from theory and
experiment”
6
“There will be opened a gateway and a road to a
large and excellent science
into which minds more piercing than mine shall
penetrate to recesses still deeper.”
Galileo (1564-1642)
(on ‘experimental mathematical analysis of nature’
appropriated here for ‘simulation science’)
7
An early visionary: L. F. Richardson
from book on numerical weather prediction (1922)
8
How well can we predict the weather?
Path of Hurricane Katrina 2005
9
Ocean
Simulations
Tsunami
SumatraAndaman
Earthquake
Tsumi.
>275,000 killed.
10
The third pillar




Computational science has been the stuff of fantasy for
generations (Galileo, Richardson, etc.)
Modern version, hosted on digital computers, has been
foreseen for about 60 years (Von Neumann, 1946)
Aggressively promoted as a national agenda for about 15
years (Wilson, 1989)
Just now beginning to earn acceptance beyond the circle
of practitioners
Experimental publication: except for the team that did the experiments,
everybody believes it
Computational publication: except for the team that did the computations,
nobody believes it.
11
The “Grand Challenges” of Wilson






A Magna Carta of high performance computing
(1989)
Supercomputer as “scientific instrument”
Attention to quality research indicators in
computational science
Sample “grand challenge” – electronic structure
Prospects for computer technology
Why the NSF supercomputer centers
12
Wilson’s burden
“In this paper, I address some of the tougher
requirements on … grand challenge research to
ensure that is has enduring value.”
 Algorithm
development
 Error control
 Software productivity
 Fostering technological advances in computers
13
Wilson’s fear
“… Often advocated is that because computers
of a fixed performance are dropping rapidly in
price, one should only buy inexpensive
computers … expecting that today’s
supercomputer performance will be achieved …
in a few years’ time. This … would be terrible…
It would violate the whole spirit of science, of
pushing at the frontiers of knowledge and
technology simultaneously.”
14
Wilson’s six examples






Weather prediction
Astronomy
Materials science
Molecular biology
Aerodynamics
Quantum field theory
15
Wilson’s six examples

Weather prediction
of dimensionality (r3 in space; r4 in time)
 chaotic behavior
 curse





Astronomy
Materials science
Molecular biology
Aerodynamics
Quantum field theory
16
Wilson’s six examples


Weather prediction
Astronomy
 need
to escape limits of observational record
 curse of dimensionality




Materials science
Molecular biology
Aerodynamics
Quantum field theory
17
Wilson’s six examples



Weather prediction
Astronomy
Materials science
 Electronic
structure problem: 3N-dimensional
 Schroedinger way behind Newton, Maxwell



Molecular biology
Aerodynamics
Quantum field theory
18
Wilson’s six examples




Weather prediction
Astronomy
Materials science
Molecular biology
 Conformation
problem combinatorial
 Protein folding “stiff”


Aerodynamics
Quantum field theory
19
Wilson’s six examples





Weather prediction
Astronomy
Materials science
Molecular biology
Aerodynamics
 Turbulence
 Full

system analysis, full envelope analysis
Quantum field theory
20
Wilson’s six examples






Weather prediction
Astronomy
Materials science
Molecular biology
Aerodynamics
Quantum field theory
 QED
is perturbative
 QCD is fundamentally nonlinear
21
A “perfect storm” for simulation
(dates are symbolic)
Applications
Hardware Infrastructure
1686
A
R
C
H
I
T
E
C
T
U
R
E
S
scientific models
1947
numerical algorithms
1976
computer architecture
scientific software engineering
“Computational science is undergoing a phase transition.” – D. Hitchcock, DOE
22
Movement towards simulation science

Standards



Publications



Tools: languages, libraries, interfaces, formats, templates
Results: validation and verification
Journals, e.g., IEEE/APS Computing in Science and Engineering
Book series, e.g., Springer’s LNCS&E
Degree programs

Approximately 50 US-based programs
http://www.nhse.org/cse_edu.html

Birds-of-a-feather meetings at conferences
23
HPCC Bluebook (1992, OSTP)


Proposed 30% increase in
federal support of HPCC (to
$638M/yr)
Four major components:




High performance computing
systems
Advanced Software
Technology and Algorithms
National Research and
Education Network
Basic Research and Human
Resources
25
It’s not just government…

200 of the “Top 500” computer systems in the world are
operated by industry
http://www.top500.org/

15 “Fortune 500” companies were sponsors of the NCSA








Banking: J.P. Morgan
Information: The Tribune Company
Insurance: Allstate
Manufacturing: Caterpillar, FMC, Kodak, Motorola
Merchandising: Sears
Petroleum: Phillips, Schlumberger, Shell
Pharmaceuticals: Lilly
Transportation: Boeing, Ford, SABRE
27
Computation vs. Theory

Computation is usually better for:
 Generality
(dimension, geometry, properties,
boundary conditions)
 Transferability of technique (to less expert users)

Theory is usually better for:
 Compactness
 Generalizability
 Insight
“The purpose of computing is insight, not numbers.” – R. W. Hamming
28
Computation vs. Experiment

Computation is usually better for:
 Economy
 Feasibility
 Latency
 Idealizations
 Safety

and/or political repercussions
Experiment is usually better for:
 Reliability
 Reality
29
Lexical soup of related terms




Computer science: the science of organizing and operating
computers, including algorithms
Information science: the science of acquiring, converting, storing,
retrieving, and conceptualizing information
Computational mathematics/numerical analysis: mathematics of
computation, esp. focused on practical difference between real
arithmetic and computer arithmetic and other resolution limitations of
computers in performing well-defined mathematical operations
Computational Science (& Engineering): the science of using
computers in pursuit of the natural science (& engineering),
especially those aspects that are not specific to a particular
discipline
30
Lexical soup of related terms, cont.


Scientific computing: a combination of computational science,
numerical analysis, and computer architecture primarily
concentrating on efficient and accurate algorithms for approximating
the solution of operator (and other) equations
Computational “X” (where “X” is a particular natural or engineering
science, such as physics, chemistry, biology, geophysics, fluid
dynamics, structural mechanics, electrodynamics, etc.): a
specialized subset of scientific computing concentrating on
techniques and practices particular to problems from “X”, together
with support technologies from CS&E
31
Clarifying examples




Computer science: architecture, systems software, data structures,
algorithmic complexity, networks, software engineering, intelligent
agents, profiling, benchmarking, performance modeling,
performance tuning
Information science: data bases, data mining, data compression,
pattern recognition
Computational mathematics: error analysis, algorithmic stability,
convergence
Computational science: scientific visualization, computational
steering, parallel partitioning and mapping, multidisciplinary
computing
32
Case studies from O’Leary (1997)

Cellular radio transmission --- placement of transmitters in building
to avoid dead spots (50% physics/engineering, 10% numerical
analysis, 40% computer science)


Image processing --- correction of Hubble images (25% astronomy,
25% signal processing, 25% mathematics, 25% computer science)


Singular value decomposition
Smoke plume modeling --- predict spread of smoke and heat in
burning building (25% physics/engineering, 50% mathematics, 25%
computer science)


Large, ill-conditioned inverse problem
Information retrieval --- latent semantic indexing of large data bases
(50% disciplinary field, 10% mathematics, 40% computer science)


Ray tracing, attenuation modeling
Large scale parallel, uncertainty quantification
What does Computational Chemistry Involve?
33
Single Processor
34
Moore’s Law
In 1965, Gordon Moore of Intel observed an exponential growth in the
number of transistors per integrated circuit and optimistically predicted
that this trend would continue. It has. “Moore’s Law” refers to a doubling
of transistors per chip every 18 months, which translates into
performance, though not quite at the same rate.
35
Prefix review

“flop/s” means “floating point operations per sec”
1,000
1,000,000
1,000,000,000
Kiloflop/s
Megaflop/s
Gigaflop/s
Kf
Mf
Gf
1,000,000,000,000
1,000,000,000,000,000
Teraflop/s
Petaflop/s
Tf
Pf
Your laptop
Lab engine
36
Pipelining

Often, an operation (e.g., a
multiplication of two floating point
numbers) is done in several stages
inputstage1stage2output


Each stage occupies different
hardware and can be operating on
a different multiplication
Like assembly lines for airplanes,
cars, and many other products
37
Consider laundry pipelining
Anne, Bing, Cassandra, and Dinesh must each wash (30 min), dry (40
min), and fold (20 min) laundry. If each waits until the previous is finished,
the four loads require 6 hours.
38
Laundry pipelining, cont.
If Bing starts his wash as soon as Anne finishes hers, and then Cassandra
starts her wash as soon as Bing finishes his, etc., the four loads require
only 3.5 hours.
Note that in the middle of
the task set, all three
stations are in use
simultaneously.
For long streams, ideal
speed-up approaches
three – the number of
available stations.
Imbalance between the
stages, and pipe filling
and draining effects
make actual speedup
less.
39
Arithmetic pipelining

An arithmetic operation may have 5 stages





Instruction fetch (IF)
Read operands from registers (RD)
Execute operation (OP)
Access memory (AM)
Write back to memory (WB)
Actually, each of these
stages may be
superpipelined further!
Time
Instructions
IF
RD
OP
AM
WB
IF
RD
OP
AM
WB
IF
RD
OP
AM
WB
…
40
Benefits of pipelining


Allows the computer to be physically larger
Signals need travel only from one stage to the
next per clock cycle, not over entire computer
41
Problems with pipelining

Must find many operations to do independently, since
results of earlier scheduled operations are not
immediately available for the next; waiting may stall pipe
Create “x”
Consume “x”


IF
RD
OP
AM
WB
stall
IF
RD
OP
AM
WB
Conditionals may require partial results to be discarded
If pipe is not kept full, the extra hardware is wasted, and
machine is slow
42
Parallelism
43
Parallelism


Often, a large group of operations can be done
concurrently, without memory conflicts
In our airplane example, each cell update involves
only cells on neighboring faces
 Cells
that do not share a face can be updated
simultaneously
No purple cell
quantities are
involved in each
other’s updates.
44
Parallelism in building a wall
Each worker has an interior “chunk” of independent work, but
workers require periodic coordination with their neighbors at their
boundaries. One slow worker will eventually stall the rest. Potential
speedup is proportional to the number of workers, less coordination
overhead.
45
Benefits of parallelism



Allows the computer to be physically larger
If we had one million computers, then each
computer would only have to do 8x109
operations per second
This would allow the computers to be about 3cm
apart
46
Parallel processor configurations
In the airplane example, each
processor in the 3D array (left)
can be made responsible for a
3D chunk of space.
The global cross-bar switch is
overkill in this case. A mesh
network (below) is sufficient.
47
SMP & MPP paradigms
Symmetric Multi-Processor (SMP)
Massively Parallel Processor (MPP)
cpu
cpu
cpu
cpu
Fast Interconnect
Mem
Mem
Mem
cpu
cpu
Shared memory
Interconnect
• two to hundreds of processors
• thousands of processors
• shared memory
• distributed memory
• global addressing
• local addressing
48
Concurrency has also grown


DOE’s ASCI roadmap
is to go to 100
Teraflop/s by 2006
Variety of vendors
engaged







Compaq
Cray
Intel
IBM
SGI
Up to 8,192
processors
Relies on commodity
processor/memory
units, with tightly
coupled network
49
Japan’s Earth
Simulator
Bird’s-eye
View of the Earth Simulator System
Disks
Cartridge Tape Library
System
Processor Node
(PN) Cabinets
Interconnection Network
(IN) Cabinets
Air Conditioning
System
65m
Power Supply
System
50m
Double Floor for IN
Cables
50
New architecture on horizon: Blue Gene/L
180 Tflop/s configuration (65,536 dual processor chips)
To be delivered to LLNL in 2004 by IBM
52
Gordon Bell Prize “peak performance”
Year
1988
1989
1990
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
Type
PDE
PDE
PDE
NB
MC
IE
MC
PDE
NB
MD
PDE
NB
NB
PDE
Application No. Procs System
Gflop/s
Structures
8 Cray Y-MP
1.0
Seismic
2,048 CM-2
5.6
Seismic
2,048 CM-2
14
Gravitation
512 Delta
5.4
Boltzmann
1,024 CM-5
60
Structures
1,904 Paragon
143 Four orders
QCD
128 NWT
179 of magnitude
CFD
160 NWT
111
in 13 years
Gravitation
4,096 ASCI Red
170
Magnetism
1,536 T3E-1200
1,020
CFD
5,832 ASCI BluePac
627
Gravitation
96 GRAPE-6
1,349
Gravitation
1,024 GRAPE-6
11,550
Climate
~5,000 Earth Sim
26,500
53
Gordon Bell Prize “price performance”
Year
1989
1990
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
Application
Reservoir modeling
Electronic structure
Polymer dynamics
Image analysis
Quant molecular dyn
Comp fluid dynamics
Electronic structure
Gravitation
Quant chromodyn
Gravitation
Comp fluid dynamics
Structural analysis
System
CM-2
IPSC
cluster
custom
cluster
cluster
SGI
cluster
custom
custom
cluster
cluster
$ per Mflops
MMflop/s
2,500
1,250
1,000
154
333 Four orders
278
of magnitude
159
56 in 12 years
12.5
6.9
1.9
0.24
54
Gordon Bell Prize outpaces Moore’s Law
CONCURRENCY!!!
Four orders
of magnitude
in 13 years
55
Problems with parallelism




Must find massive concurrency in the task
Still need many computers, each of which must
be fast
Communication between computers becomes a
dominant factor
Amdahl’s Law limits speedup available based on
remaining non-concurrent work
56
Amdahl’s Law (1967)
In 1967 Gene Amdahl of Cray Computer formulated his famous
pessimistic formula about the speedup available from
concurrency. If f is the fraction of the code that is parallelizable
and P is the number of processors available, then the time TP to
run on P nodes as a function of the time T1 to run on 1 is:
T1
TP  f  (1  f )T1
P
T1
1
Speedup  
TP (1  f )  f / P
1
lim Speedup 
P 
(1  f )
Speedup
10000
1000
f = 0.8
f= 0.9
f = 0.95
f = 0.99
f = 0.999
f = 1.0
100
10
1
4
16
64
246
1024
Number of processors
57
Algorithms
58
Algorithms are key
“I would rather have today’s algorithms on
yesterday’s computers than vice versa.”
Philippe Toint
59
The power of optimal algorithms


Advances in algorithmic efficiency can rival advances in
hardware architecture
Consider Poisson’s equation on a cube of size N=n3
Year
Method
Reference
Storage
Flop
1947
GE (banded)
Von Neumann & Goldstine
n5
n7
1950
Optimal SOR
Young
n3
n4 log n
n3.5 log
1971
CG
Reid
n3
1984
Full MG
Brandt
n3

64
64
2u=f
64
n
n3
If n=64, this implies an overall reduction in flop of ~16 million
*
*Six-months is reduced to 1 s
60
Algorithms and Moore’s Law


This advance took place over a span of about 36 years, or 24
doubling times for Moore’s Law
22416 million  the same as the factor from algorithms alone!
relative
speedup
year
61
Computational Limitations:
Triple-finiteness of computation

Finite wordlength
A 64-bit word can represent how many numbers?
264=(210)6 24~16x(103)6=16x1018 (IEEE floating point allocates 53
of these bits to the mantissa)

Finite wordlength
A 64-bit architecture typically addresses about 1015 distinct words
of memory – this is small compared to, e.g., Avogadro’s number

Finite number of operations
•
A typical computation can get at most a few days on a teraflopsclass machine, or about 1017 flops
62
Implications of triple-finiteness



Computational resolution fundamentally limited
Computational accuracy fundamentally limited in
a way that some computations that appear to be
achievable are not, because of sensitivity to
arithmetic error
High-performance computing has growth
potential in an employment sense 
63
Computational Difficulties:
Conditioning, accuracy, stability

Problem is ill-conditioned if a small change in the input data can
make a large change in the output



characteristic of the problem, not of the process
in severe cases, no algorithm can help
Process is unstable if the result it produces is sensitive to floating
point errors made during its execution

characteristic of the process, not of the problem
 another algorithm may help

Only if a stable algorithm is applied to a well-conditioned problem
may an accurate result be expected


If either stability or accuracy is missing the computation may be a waste
of time and the result misleading
We avoid at present the subject of nonuniqueness

Important in nonlinear problems
64
Applications
65
Today’s “terascale simulation”
Applied
Physics
radiation transport
supernovae
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Engineering
crash testing
aerodynamics
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation
is an important complement to experiment.
66
Today’s “terascale simulation”
Applied
Physics
radiation transport
supernovae
Experiments
controversial
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Engineering
crash testing
aerodynamics
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation is an
important complement to experiment.
67
Today’s “terascale simulation”
Experiments
dangerous
Experiments
controversial
Applied
Physics
radiation transport
supernovae
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Engineering
crash testing
aerodynamics
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation is an
important complement to experiment.
68
Today’s “terascale simulation”
Experiments prohibited or
impossible
Experiments
dangerous
Experiments
controversial
Applied
Physics
radiation transport
supernovae
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Engineering
crash testing
aerodynamics
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation is an
important complement to experiment.
69
Today’s “terascale simulation”
Experiments prohibited or
impossible
Experiments
dangerous
Experiments
controversial
Applied
Physics
radiation transport
supernovae
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Experiments difficult
to instrument
Engineering
crash testing
aerodynamics
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation is an
important complement to experiment.
70
Today’s “terascale simulation”
Experiments prohibited or
impossible
Experiments
dangerous
Experiments
controversial
Applied
Physics
radiation transport
supernovae
Environment
global climate
contaminant
transport
Biology
drug design
genomics
Experiments difficult
to instrument
Engineering
crash testing
aerodynamics
Experiments
expensive
Scientific
Lasers & Energy
combustion
ICF
Simulation
In these, and many other areas, simulation is an
important complement to experiment.
71
Examples: multiple-scale applications

Biopolymers, nanotechnology
 1012 range in time, from 10-15
sec (quantum fluctuation) to 103 sec


(molecular folding time)
typical computational model
ignores smallest scales, works
on classical dynamics only, but
scientists increasingly want
both
Galaxy formation
 1020 range in space from

binary star interactions to
diameter of universe
heroic computational model
handles all scales with localized
adaptive meshing
Supernova simulation, c/o A. Mezzacappa, ORNL

Supernovae simulation

massive ranges in time
and space scales for
radiation, turbulent
convection, diffusion,
chemical reaction, nuclear
reaction
72
Parallel Computation: Discretization of Space (Grid)
Construct “grid” of triangles
Construct “control volumes”
surrounding each vertex
Compute effluxes
Compute influxes
Compute internal sources
Finally, sum all fluxes and sources (with proper sign) and
adjust value at vertex; then loop over all such vertices.
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Adaptive Cartesian mesh
inviscid shock
near field
far field
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Adaptive triangular mesh
viscous boundary layer
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Unstructured grid for complex geometry
slat
flaps
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Scientific visualization adds insight
Computer becomes an experimental laboratory, like a
windtunnel, and can be outfitted with diagnostics and
imaging intuitive to windtunnel experimentalists.
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What would scientists do with 100-1000x? Example: predicting future
climates

Resolution

refine horizontal from 160 to 40 km
 refine vertical from 105 to 15km

New physics

atmospheric chemistry
 carbon cycle
 dynamic terrestrial vegetation (nitrogen and sulfur cycles and landuse and land-cover changes)

Improved representation of subgrid processes

clouds
 atmospheric radiative transfer
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What would scientists do with 100-1000x? Example: predicting future
climates
Simulations at various resolutions using the Los Alamos Parallel Ocean Program (POP) have demonstrated that, because
equatorial meso-scale eddies have diameters ~10-200 km, the grid spacing must be < 10 km to adequately resolve the eddy
spectrum. This is illustrated qualitatively in the set of four images of the sea-surface temperature (SST). Figure (a) shows a
snapshot of SST from satellite observations, while the three other figures are snapshots from the POP simulations at
resolutions of (b) 2, (c) 0.28, and (d) 0.1. The narrow, meandering current off the coast of Japan is the Kuroshio Current
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Parallel Computation: N-body problem

Examples:

Molecular Mechanics
 Galaxy Modeling
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