Chem-Bio Informatics for Physicists
A note for lectures that will be delivered under auspices of Institute of Physics, National Center for
Natural Science and Technology during 25-29 November, 2002 in Hanoi and under auspices of Center for
Bio-Medical Physics during 2-4 December in Ho Chi Min City, Vietnam
By Tsuguchika Kaminuma, Ph.D. (kaminuma@cbi.or.jp)
Official Address
Tsuguchika Kaminuma,
Rm 301, Iida Building, 4-3-16 Yoga, Setagaya-ku, Tokyo, 158-0097, Japan
Phone 81-3-5491-2403, FAX 81-3-5491-5462
e-mail: kaminuma@cbi.or.jp
Curriculum vitae of Tsuguchika Kaminuma
Dr. Kaminuma is currently working as a freelance researcher. He is also a board member of Chem-Bio
Informatics Society and the president of his own company, Biodynamics, Inc.
Dr. Kaminuma was born in Kanagawa Prefecture, Japan in 1940. He finished undergraduate work at
International Christian University in Tokyo in 1964, received a Master of Science degree in Physics from
Yale University in 1966 and Ph.D. in Physics from University of Hawaii in 1970. He worked on Pattern
Recognition as a research assistant to Prof. Michael Satoshi Watanabe during 1966-1971 at University of
Hawaii. He worked on computer application to biomedicine at a Laboratory of Hitachi Inc. (1971-1976),
at Tokyo Metropolitan Institute of Medical Science (1976-1989), and at National Institute of Medical
Sciences (1989-2001). He retired from National Institute of Medical Science in March 2001. He had
taught several universities including University of Yamaguchi, University of Tokyo, University of Tokai,
and Nara Advanced Science and Technology Graduate School. He founded Chem-Bio Informatics Society
and its journal, and worked for IPCS(International Program on Chemical Safety) of WHO as a coordinator
of Japanese researchers and a Program Advisory Board member. He published many research papers and
wrote books in both Japanese and English.
1
Contents
Introduction
Session 1. Views of Life
Session 2. Role of Physics in Modern Biology
Session 3. Sequence, Sequence, and Sequence!
Session 4. 3D Structure of Biomolecules
Session 5. Modeling Cell World
Session 6. Frontiers of Bio Sciences
Session 7. Quest for Drugs and Safety Control of Chemicals
Session 8. Genome Based Clinical Medicine
Session 9. Collaborative Projects
Chapter 10. Books for Physicists who are interested in biology
Appendix
Introduction
Why I give these lectures?
In 1981 I founded a multidisciplinary research society called the Chem-Bio Informatics Association that
now becomes the Chem-Bio Informatics Society. The member of this society consists of researchers from
universities, national institutions, and industry laboratories. Area of interest of this society covers;
1. Molecular Computing
2. Molecular Recognition
3. Bioinformatics and Computational Biology
4. Data Analyses of Genome Wide Experiments
5. Information and Computing Infrastructure for Pharmacology and Toxicology
6. Disease Modeling
7. Other topics including emerging IT and wet technologies.
It offers monthly seminars, organize annual meetings, and publish an online journal called CBI Journal.
Computational Chemistry and Bioinformatics
Though “bioinformatics” becomes very popular, we have emphasized the importance of this discipline in
addition to molecular computing. Molecular computing is the heart of computational chemistry that has
been ever accelerated by rapid advance of computing power. In fact bioinformatics deeply relates to
molecular computing, and these two disciplines play vital roles in advancing;
1.
2.
3.
4.
Biological Sciences
Drug Development via Computer-Aided Drug Design
Safety Control of Chemicals via Computational Toxicology
Environmental Problems such as bioremediation and clean energy.
Many leading computer companies look biomedical field as the next big market and their target, and a
new word “BioIT” was coined.
Possible Research Projects in Vietnam
If we consider chemical computing and bioinformatics in Vietnam, two important subjects emerges;
2
1. Computational Toxicology for dioxin and other chemicals
2. Biochemical Prospecting
There may be no question about the importance of the first subject. The second subject may need some
explanation. By biochemical prospecting I mean research for searching useful chemicals and useful
biological organisms that contains useful chemical ingredients or offer useful materials for food, drug, or
other means. Medicinal plants and useful plant hunting are good examples of this research.
In Japan the so called Chinese Traditional Medicine is still used routinely. The problem of Chinese
Traditional Medicine is its complex ingredients and the lack of evidence in modern medical sense. All
drugs admitted in modern regulation are of single ingredient. Even a drug consist of single chemical may
hit multi-targets (biomolecules). Therefore is extremely difficult to prove the effects of multi-chemical
agents by modern laboratory experiments and clinical trails.
Same problem exists for proving efficacy and danger (side effects) of foods, designer foods (functional
foods), and supplements. However methodologies developed in the field of rational drug design are
gradually getting into these neighboring sciences. Two research groups one in Singapore and one in China
recently published papers on these problems. However because of the emerging powerful techniques of
genome information and genome wide simultaneous measurements by gene chips, proteomics, and
metabolonomics, it becomes realistic to attack these problems scientifically.
But for that you must
1.
organize multi-disciplinary research team consists of both wet experiment expertise and
theoretical and computational specialists of chemical computing and bioinformatics.
2.
assemble good hardware and software tools and integrate them into powerful infrastructure of
your research
3.
have good contact with advanced research groups.
My lecture may gives you basic knowledge for you to think about such projects and the CBI Society
members will be a good future potential collaborators of these projects.
Purpose of this Lecture
1. Introduce physics graduate students and researchers in other fields to emerging biological sciences and
technologies, and show them that there are a lot of interesting problems that can be approached by those
who have sound background in theoretical model building and computation.
2. Introduce informational and computing resources in computational chemistry, bioinformatics, biological
computing, and biomedical sciences and how to utilize them.
3. Stimulate collaborations between experimental researchers and theoretical researchers in biosciences
and biotechnologies in order to start new projects in Vietnam.
4. Suggest further collaboration of the participants with the members of The Chem-Bio Informatics
Society in Japan, and give hints on planning projects for Vietnam researchers.
Lecture Materials and references
Almost all of the lecture materials are selected from world wide websites, edited, and put on the web site
of the Chem-Bio Informatics Society website (www.cbi.or.jp/exp/cbi/vietnam/02_lecture). Participants are
recommended to download the lecture materials prior to attend the lectures. The highly recommended
materials are marked by “$”.
3
Basic Materials
Following materials are selected as the most basic for my lecture. They are reading
assignment materials.
1, Introduction to modern biology
The Road to DNA (down load from web$)
MIT Biology Hypertext, Chap. Chemistry Review, Large Molecule, Cell Biology, Central
Dogma, Prokaryote Genetics and Gene expression (down load from web$)
2. Developing Chemical Databases
Nakano’s note on Chemical Database (e-mail)
X. Qiao, and others, A 3D Structure Database of Components from Chinese Traditional
Medical Herbs (paper copy, send by EMS)
Kaminuma, Vietnam Medicinal Plant DB (will bring)
3. Molecular Calculation
NIH Molecular Model Tutorial (web$)
Introduction to Macromolecular Simulation (web$)
CHARMM Tutorial (web$)
Papers on Fragment Molecular Orbital Method (e-mail)
4. Bioinformatics
Bioinformatics Tool Guide (e-mail)
Use’s Guide to the Human Genome (web$)
5. ADME-Tox and Computational Toxicology
LCBRA (web$)
Koyano’s paper on dioxin (web$)
ADME QSAR L.Afzelius and S. Eikins papers (web$)
6. Computer-aided Drug Design
National Institute on Drug Abuse Research Monograph Series 134, Medincation
Development: Drug Discovery, Database, and Computer-Aided Drug Design (web$)
R. Abagyan’s paper (copy send), H.A. Carlson’s paper (web$)
7. PHII Project
Kaminuma/CBI (e-mail)
Univ. of Singapore, Bioinformatics Group (web$)
X.Chen, CLiBE paper (paper copy)
8. Pathway/Network to Disease
Nuclear Receptor dependent pathways and networks (e-mail)
9. C.elegans
4
CERS (web, OHP)
Session 1. Views of Life
Biologist’s and Chemist’s View of Life
The Cell Theory
All living organisms are built up of cells.
1839 Microscopy observation by Schleiden and Schwann (German)
1860 Hereditary transmission through the sperm and egg.
Mendelian Laws
Discovery of Genes: Each gene can exist in variety of different forms called alleles. A gene for each
hereditary trait is given by each parent to each of its offspring. Later it was found that the physical basis
for this behavior is in the distribution of homologous chromosomes during meiosis.
1865 Gregor Mendel published his work
1900 William Bateson rediscovered Mendel’s work.
Theory of Evolution
Darwin’s and Wallace’s theory of evolution by natural selection:
Today’s complex plants and animals are derived by a continuous evolutionary progression from first
primitive organisms.
Alfred Russel Wallace (British)
1859
Charles Darwin, Origin of Species
Genetic information is contained in, and transmitted by, DNA.
1943
Owald Avery (Canadian/America) used pneumonia bacterium.
X-ray Crystallography
1912
Bragg solved structure of NaCl at Cabendish Lab.
1937 Max Peruz started hemoglobin analysis under Bernal
1947
Kendrew started muscle protein myoglobin
1951 Pauling proposed helical configuration (later called alpha helix) would be important element in
protein structure.
1953
Complementary Double Helix Structure Model of DNA by Crick and Watoson
1959 First protein structures were solved by Peruz and Kendrew Technological Breakthrough
In 1953 an essential breakthrough occurred in X-ray crystallography that the attachment of heavy atoms to
protein molecules could logically lead from the diffraction data to correct structures.
Advances of electronic computers enabled to carry heavy calculations required for crystallographic data
analysis.
A Physicist’s view
1943 Series of lectures at Trinity College in Dublin
Erwin.O. Schrodinger, What is Life ?, Cambridge Univ. Press, 1944
His book recruited many brilliant young physicists to biology after the war. The book still stimulates many
researchers who have theoretical mind including biologists like Gerald Edelman.
5
A Mathematician’s view
All that can be calculated can be calculated by a Turing Machine.
Alan Turing, Turing Machine as a Model of Computer
An Informatics view
Self-reproducing machine needs a long tape like DNA or RNA. Biological organisms are just like
molecular Turing machines!
John von Neumann (Complied by Arther W. Burks), Theory of Self-Reproduing Automata, University of
Illinois Press, 1966,
Role of Experimental Physics in Modern Biology
Measurement of Structures of Living Systems
Optical Microscope (Nomarski Optics), Electron Microscope
X-ray crystallography
SOR (Synchrotron Orbital Radiation)
NMR (Nuclear Magnetic Resonance)
Mass Spectroscopy(MS), AMS (Accelerated MS)
Classification of Life
Taxa : Eucaryotes (fungi, plants, animals), Archae, Eubacteria
Procaryote vs. Eucaryote
Uni-cellular organism vs. Multicellular organism
Model organisms
Bacteria/E.coli(Escherichia coli), Yeast(uni-celluar eucaryote), Worm/C.elegans(Caenorabditis
elegans), Fly/Drosophila melanogaster, Vertabrate/Zebrafish and Puffish?, Mammalian/Rat and Mouse,
Plants/Alabidopsis thaliana and Rice, Homo sapiens/Human
Molecules in Life
There are four basic types of macromolecules in life.
Sugars, fatty acids, amino acids, nucleotides
Structures in Cells
Membrane
Cytoplasm
Nucleus
Mitochondria/Chlorophyll
Functions of Cells
Genome, the programming codes of cells
Protein Synthesis: Transcription and translation of the genetic codes
DNA Replication
Other biosynthesis and metabolism
6
Energy Conversion
ATP is the currency of various bio-energies.
Molecular Communications
Phosphorylation by kinase vs. diphosphorylation by phosphatase
References and Reference Sites
MIT Biology Hypertextbook
NIGMC Digital Textbooks on Life Sciences
DOE Primer on Molecular Genetics
WWW Virtual Library of Cell Biology
The American Society for Cell Biology
Cell Biology Education
B. Alberts et al. , Molecular Biology of the Cell, Garland, 1994
B. Alberts et al. Essential Cell Biology: An Introduction to the Molecular Biology of the Cell, Garland,
1998
Session 2. Molecular Computation
Molecular Representations
Molecular Registration
CAS No : Chemical Abstract Service Registry Number
Molecular Formula and Molecular Drawing
ChemDraw
3D atomic coordinates and Molecular Graphics
CCDC(Cambridge Crystallographic Data Center)
RasMol
Molecular Structure and Nomenclature
MDL, ISIS
ChemFinder
Chemical/Molecular Database
Molecular Computation
What can we compute?
Structure and Reactivity
Big Commercial Vendor: Accelrys
Classical models : Molecular Mechanics
AMBER : Force Field Caluculation
Macro Model/MOPAC:Schrodinger
Quantum chemistry: semi-empirical and ab initio MO methods
MOPAC
GAMESS
GAUSSIAN
FMOM : Fragmented Molecular Orbital Method
Molecular Dynamics
7
CHARMM
Reference Sites
WWW Computational Chemistry Resources
NLM Chemical Information
Exercises for Session 2
I. Developing a chemical database and put it on the web.
Find some examples of chemical databases that have 3D structure data.
Drug Database
Carcinogenic chemicals
Endocrine Disruptors
Attribute of chemicals
Names and ID numbers, CAS Registry Numbers
Molecular formula and structure representation
3D atomic coordinates
Generate all possible structures of the dioxins.
EXCEL to ACCESS
Put chemical database on the web.
A Chemical database of Vietnam Medicinal Plants
Session 3. Sequence, Sequence, and Sequence!
Life and Computer
Similarity and difference of living organism and computer
The Central dogma of molecular biology
Computer is a Turing Machine
A history of interference between computer technology and life science
Genome-The Code of Life: Success of The Human Genome Projects
Advances of sequencing technology
The first complete sequencing of virusφX174 genome
Sequencing of Model Organisms
Where can we find the genome sequence data and how to use that?
There are rich public resources available on the web. These resources cover
DNA and RNA sequence data and their 3D structural data
Protein (amino acid) sequence data and their 3D structural data
Lipid, sugar, and other carbonhydorate molecular data
and their analyses tools.
Good references to how to use human genome data and sequence informatics are the followings:
A User’s Guide to the Human Genome, Nature Genetics
David W. Mount, Bioinformatics, Cold Spring Harbor Laboratory Press, NY, 2001
Bioinforamtics emerged from sequence data analyses. Main problems are how to extract informative
feature such as regions that code proteins from sequence data, how to compare two sequences and
measure their similarity, and how to find similar sequences
(homology search, Smith-Waterman
8
algorithm).
In human genome projects how to store rapidly increasing sequence data, how to align sequence
fragments into longer sequences (particularly for shot gun approach), how to annotate sequences become
challenging theme for bioinfomaticians.
Since sequence is nothing but code computer is very fit for such problems.
Session 4. 3D Structure of Biomolecules
Protein Structure: PDB
The Protein Data Bank is the most well-known public data source for 3D atomic coordinates of proteins
and other bio macromolecules such as nucleic acids.
Structure Genomics-A Post Genome Challenge
The number of representative protein structure was estimated to be approximately 10,000. The Structure
Genomics Project aim to determine all of these structures by international collaboration.
Molecular Graphics and Modeling for Biomolecules
UCSF Computer Graphics Lab
UIUC Theoretical Biophysics Group
NIH The Center for Molecular Modeling
Docking Study of Xenobiotic Chemicals and Target Biomolecules
AutoDock : The Scripps Research Institute
Peptide-Protein Interaction
SDSC has powerful computing facilities and provides useful software tools. Example of the latter is a
peptide and protein docking study program DOT. This program needs cluster computer.
DOT : San Diego Super Computer Center (SDSC)
.
Simulation of Protein Folding and IBM Blue Gene
Protein folding simulation is a grand challenge for molecular simulation and chemical computing. IBM
announced to challenge this problem by developing a new powerful computer called Blue Gene.
Exercises for Session 3 and 4
Sequence and 3D structure problems are deeply related. So here we give mixed exercises for these two
topics.
The goals of these exercises are;
(1) get acquainted with public resources of sequence data and their analyses tools,
(2) access to these databases and use some analyses tools provided these websites.
Search a protein sequence and its gene sequence.
9
Examples of proteins:
GPCR
PKC(Protein Kinase C),
Estrogen Receptors(alpha and beta), PPAR, RXR
Ah Receptors and their genes
Find amino acid sequences, genes, cDNAs, DNA coding regions(exons) of these proteins.
Try a homology search tool such as BLAST or FAST,
Are there any 3D structure data of these proteins? Search PDB and show them graphically.
Protein structure modeling
Modeling Nuclear Receptors
Human CYP2C9 modeling from rabbit CYP2C5
Find ligand-protein complex structures in PDB, and examine hydrogen bonds and so on.
Session 5. Modeling Cell World
Genome Wide Simultaneous Measurements
DNA chip and Microarray
Proteomics
Metabolomics/Metabonomics
Protein-Protein Interactions
Genome Wide Data Analyses Tools
GeneSpring
Mapping Molecular Interactions
Biochemical Synthesis and Metabolism Maps
Gerhard Michal ed., Biochemical Pathways-Atlas of Biochemistry and Molecular Biology, John
Wiely, NY, 1999
Cell Signaling Pathways and Networks
Cell Simulator : Virtual Cell
Systems Theory
Eberhard O. Voit, Computational Analysis of Biochemical Systems-A practical Guide for Biochemists
and molecular Biologists, Cambridge Univ. Press, 2000
Exercises for Session 5
Go NCBI and find real data of gene chip experiments.
Go Boerhinger Mannheim, EcoCyc/MetaCyc, KEGG, WIT/EMP, PathDB and examine the maps.
Go NIHS website and look for RDB and CSNDB.
10
Examine what kind of signal transductions are related to cancer?
Examine what kind of singnal taransductions are related to development?
Wnt, TGF-beta, Hedgehog,…
Find all signal pathways started from insulin receptor, and find their ligands and their possible effects.
Find some works/papers that analyses genome wide experimental data by mapping to pathway/network
maps.
Session 6. Frontiers of Bio Sciences
Comparative Genomics
Developmental Biology-The True Mystery of Life
Development: The process from zygote to adult
Two big events in life - gastrulation and neurulation
C.elegans the most known multicellular organism
Organoregenesis /Regeneration Medicine
D’Arcy W. Thompson, On Growth and Form (two volumes), Cambridge, 1917
J.M.W. Slack, From Egg to Embryo-Regional Specification in Early Development (2nd ed.), Cambridge
Univ. Press, 1983
Scott F. Gilbert, Development Biology 6th edition, Sinauer Associate, 2000
Lewis Wolpert, Principles of Development 2nd, Oxford Univ. Press, 2002
Endocrine System
National Cancer Institute Tutorial: Tamoxiphen and Raloxiphen
Endocrine Disruptor Hypothesis
C. Colborn et al, Our Stolen Future
Endocrine Disruptor Information for Researchers, NIHS Japan
(www.nihs.go.jp/hse/endocrine-e/index.html)
IPCS, Global Assessment of the State-of-the-Science of Endocrine Disruptors
Chemical Database for Endocrine Disruptors
Neural System and Brain
Eric R. Kandel, James H. Schwartz, and Thomas M. Jessell, Principles of Neural Science 4 th edition,
McGraw-Hill, 2000
Immune System
National Cancer Institute Tutorial: Understanding the Immune System
Alan S. Perelson and Gerard Weisbuch, Immunology for physicists, Reviews of Modern
Physics, Vol. 69, Nov. 4, October 1997, pp.1219-1267
Science of Cancer
NCI Tutorial
Abnormal cell proliferation
Apoptosis – Program cell death
Chemical Carcinogen
NCI Database
11
FDA (www.fda.gov/cvm/guidance/G3ptg.html)
IARC (International Agency for Research on Cancer) Monographs
Session 7. Quest for Drugs and Safety Control of Chemicals
PHII Project
Pharmaceutical Informational and Computing Infrastructure
CBI Journal Vol.1 No. 1
Drug Databases
JAN /Japanese Pharmacopoeia
USAN
INN
Drugness and Drugability Analyses
CBI Journal Hirayama’s Paper
Good effects and bad effects are two sides of the same coin.
ADME : Absorption, Distribution, Metabolism, Excretion
Fate of Drugs and Xenobiotic Chemicals in living organisms
Drug Metabolism Enzymes: Cytochrome P-450
Transporters
Toxicity Prediction: e-Tox
QSAR: TOPKAT, MultiCASE, ToxSYS
Knowledge-based: DREK, HazardExpert, OncoLogic
Internal Targets of Xenobiotic Chemicals
QSAR when the targets are unknown
Applicaton of Tripos/CoMFA to dioxins: Paper by T. Koyamo et al.
Target hunting – search for disease related genes
International Human Genome Sequencing Consortium, International sequencing and
of the human
genome, Nature, Vol.409, 15 February, 2001,(pp.912 Drug Targets)
The Concept of Receptors and Ligands
Receptor Database
Drug Target Database
Focused Library
Binding Affinity Database
Docking study when the targets are known
AutoDock, DOT
Virtual Screening – Computer aided HTS
12
Ruben Abagyan’s Paper
(http://abagyan.scripps.edu/lab/web/man/frames.htm)
Computational Toxicology
The website of Laboratory of Computational biology and Risk Analysis at NIEHS explains new
approach to computational toxilogy.
National Library of Medicine: Toxnet (toxnet.nlm.nih.gov/)
Philip Wexler (www.nnlm.nlm.nih.gov/psr/toxnet.html)
National Center For Toxicological Research/Center for Computational Toxicology
National Institute of Environmental Health Sciences, Endocrine Disruptor DB
QSAR DB for Endocrine Disruptors
Koyano et al., QSAR of Dioxin by CoMFA, CBI Journal
Zacharewski Laboratory: In Silico Toxicology
Session 8. Genome Based Clinical Medicine
From Cell Models to Physiological Models
Large Scale Biology Corpotation
Cancer: Gene Network Scinces
Cardio Vascular Disease: Physiome Science
Obesity, Diabetes: Entelos
Immunological Diseases: ISB (Institute of Systems Biology)
Genetic Variation and Personalized Medicine
SNPs/Micro Satellites
Pharmacogenomics and FDA Policy
Ongoing Research: NR and Disease Modeling: Kaminuma/CBI
Session 9. Collaborative Projects
In this last session I would like to propose some ideas on further collaboration between Vietnam
researchers and Japanese researchers who are members of the Chem-Bio Informatics Society. The two
collaborative projects described bellow are deeply interrelated. I think the most important resources for
these projects are talented and well-trained researchers. I see great hope on your group in this aspect.
1. CBI Grand Challenges
Right now I am still an active member of the Society I founded, the Chem-Bio Informatics Society.
Supported by 37 industries (mostly pharmaceutical and computer industries) the society is growing its size
and its influence among both academic and industry sectors in Japan. The society is going to organize its
fourth annual meeting in Tokyo during 17-19 September. I suggest that your group may establish similar
nonprofit, research-oriented, academic, industry and government complex. Such a complex may
contribute not only to scientific community but also industry and business of Vietnam. Your group may
send some of your researchers to the CBI Society member researchers for training and collaboration on
the following topics:
(1) Large scale molecular computing
Programming for Fragment MO Method
PC/Linux Clusters, Grid Computing
(2) Chemical substance databases and QSAR
13
(3) Virtual Screening: Focused Library and Docking Study
(4) Micro AI: Genome Wide Measurement Data Interpreter
(5) Disease Modeling: such as obesity or diabetes
(6) Computational Toxicology: for dioxins and other chemicals
The Society’s home page (www.cbi.or.jp) was poor in its content, but it will be more enriched in the
future.
2. Biochemical Prospecting
The word “Chemical Prospecting” means to search useful natural chemical such as ingredients of
medicinal plants. By “Biochemical Prospecting” I mean the research project to search useful plants and
other organisms such as marine organisms and their useful chemical components. In addition to medicinal
plants food industries are now looking “Functional Foods” or “Designer’s Foods” that contain active
compounds proved to be good for human health.
Last December when I visited Hanoi I had interesting discussions with
Dr. Le Thi Xuan on medicinal plant hunting. I set as our first collaborative goal to produce digital files on
Vietnam medicinal plants based on the two books. The first book is the English two volumes book which
Dr. Le Thi Xuan gave me(National Institute of Material Medica/LuVan Truyen and Nguyen Gia Chan eds.,
Selected Medical Plants in Vietnam Vol.I and II, Science and Techonology Publishing House, Hnoi, 1999),
and the second one is a Vietnam Traditional Medicine book (Nhungcay Thuoc Va Vi Thuoc Vietnam,
1995) which Mr. Hidaka showed me. Now I asked some of my assistants to produce digital files that
consist of Latin and Vietnam names, source plant names and structures of chemicals contained in the two
books. We could not input Vietnam characters neither could we input the English text. We did this work as
just a trail, and would like to leave addition works for Vietnam colleges if possible. Since our files are
only for internal use, we did not care for the copyright at this time, but I am interesting to discuss with the
publishers to get the permission to use them in future.
In a wider perspective this kind of work will be categorized into what is called “chemical
prospecting” or “biochemical prospecting” which search useful natural products. I am very much
interesting in this subject but unless we have enough fund it is unrealistic to pursue such a project. So I
have been trying to get some government funds for this topic but so far I did not have succeeded.
Some websites that we considered important on this subject are linked at the CBI Society Home
Page that includes:
・ WHO Report on Traditional Medicine
・ Commercial Companies successfully working on this subject
・ Asian research groups working on this subject
・ Traditional Medicine and Medicinal Plants in Cuba
Their information is highly useful.
Supplementary Comments
Infrastructure building
In order to carry research efficiently you need good infrastructure of hardware and software.
1. For hardware you need good computational machines that may be PC (Window) clusters or PC based
Linux clusters. You must train some of your computational scientists for this task.
2. It is best to look for good freewares or academic use softwares first. It may needs some skills to install,
14
adjust, and assemble these softwares for specific tasks. You must assign some good people for this
mission and give them enough time to learn.
3. It is important to consider how to adapt for technological advances. Algorithms remain alive
relatively long time, but hardware changes most rapidly, and software follows that. Thus you will
always face with the problem of updating your systems and computational environments.
4. It is a good idea to collaborate with information specialists and informatics researchers on this subject.
5. Network environment is one of the most important factors for collaboration. You must assign good
people for this service work.
Collaboration with Experimental Groups
1, Theoretician can not work alone in these fields. Good collaboration with good experiment groups is the
key of producing good research results. Your collaborator may be synthetic chemists, molecular
biologists, toxicologists, or medical researchers both of basic and clinical.
2. You may consider to set up some “ informational and computing support center” for experimental
groups. At such center you can concentrate rare human resources and let them work effectively for
experimentalists. Network is again the key for such a support and collaboration center.
How to start and how to continue?
1. Best way to start is to attack specific problems in collaboration.
2. I suggest the following them as start up theme.
(1) Development of medicinal plants in Vietnam and their component chemicals database.
(2) Computational toxicological approach to dioxins and other hazardrous chemicals. Development
of basic chemical database, study QSAR of these chemicals, and develop pathway/network
databases for studying effects of these chemicals on biological systems.
(3) Informatics and computational approach to food safety and functional food design.
Chapter 10. Books for Physicists who are interested in biology
Below is Kaminuma’s personal collection of books that are highly recommendable for physicists who are
interested in life. These books touch on such important and fundamental topics as how physicists should
approach to biology, life as computing machine, life as developing machine, and how life accumulated
these kinds of properties through long history of evolution.
John Maddox, What Remains To Be Discovered, Macmillan, London, 1998
Freeman Dyson, The Future of Physics, Physics Today, 1970, also in F. Dyson, From Eros to Gaia,
Pantheon Books, NY, 1992, pp.151-159
John von Neumann, The Computer and the Brain, Yale Univ., New Haven, 1958
Manfred Eigen and Ruthild Winkler, Laws of the Game-How Principles of Nature Govern Chance,
Princeton Univ. Press, 1993 (translated from German edition, Naturgesetze steuern den Zufall, R. Piper &
Co., Verlag, Munich, 1965)
Richard P. Feynman (J.G. Hey and R.W. Allen eds.), Feynman Lecture on Computation, Addison Wesley,
15
1996
Richard P. Feynman, There’s Plenty of Room at the Bottom, A Talk to American Physical Society on
December 29, 1959 at Caltech, also in Richard P. Feynman (Jeffery Robbins ed.), The Pleasure of Finding
Things Out, Perseus Pub., 1999, pp.117-139
Murray Gell-Mann, The Quarks and the Jaguar-Adventures in the Simple and the Complex, Little, Brown
and Company, London, 1994
Stuart Kauffman, AT HOME IN THE UNIVERSE-The Search for the Lawsof
Self-Organization and Complexity, Oxford Univ., 1995
Peter Coveney and Roger Highfield, Frontiers of Complexity-The Search for Order in a Chaotic World,
Random House, NY, 1995
Levin Kelly, Out of Control-The New Biology of Machines, Fourth Estate Limited, London, 1994
Roger Penrose, The Emperor’s New Mind-Concerning Computers, Minds, and Laws of Physics, Oxford
Univ. Press/Penguin Books, 1989
Roger Penrose, Shadows of the Mind, Oxford Univ. Press, 1994
John H. Holland, Hidden Order-How Adaptation Builds Complexity, Addison-Wesley, 1995
Ian Stewart, Life’s Other Secret-The New Mathematics of the Living World, Penguin Books Ltd., London,
1998
Richard Dawkins, The Selfish Gene (new edition), Oxford Univ. Press, NY, 1989 (First edition in 1976)
Richard Dawkins, the extended phenotype-The long reach of the gene, Oxford Univ. Press, 1982
Richard Dawkins, The Blind Watchmaker-Why the evidence of evolution reveals a universe without
design, Norton, 1987
Christopher Wills, The Wisdom of the Genes-A New Pathway to Evolution, HarperCollins, 1989
Robert J. Richards, The Meaning of Evolution, University of Chicago Press, 1992
George C. Williams, Natural Selection-Domains, Levels, and Challenges, Oxford Univ. Press, 1992
Stephen Jay Gould, Wonderful Life-The Burgess Shale and the Nature of History, Norton, NY, 1989
Stephen Jay Gould, Life’s Grandeur-The Spread of Excellence from Plato to Darwin, Random House,
1997
Simon Conway Morris, the Crucible Creation-The Burgess Shale and the Rise of Animals, Oxford Univ.
Press, 1998
16
Appendix
1. Where can you study bioinformatics ?
2. New Topics in Informatics and Computing
3. Food Safety and Health Centers
17