history of copmuters in pharmaceutical development and research

1. Presented by,
Pratiksha C Chandragirivar
M pharma 1st sem
Dept. of pharmaceutics
HSK COP Bagalkot
Facilitated to,
Dr. Laxman Vijapur
Assistant professor
Dept. of pharmaceutics
HSK COP Bagalkot
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2. Contents:
1. Introduction
2. Computational chemistry : the beginnings at Lilly
3. Germination:1960s
4. Gaining the foothholds:1970s
5. Growth :1980s
6. The fruition : 1990s
7. References
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3. Introduction :
Nowadays, computers are omnipresent in pharmaceutical
research and development.
It is hard to imagine when there were no computers to assist the
medical chemist or biologist.
A quarter - century ago , there were no clue of computers on
the desk of scientist and company manager.
Now, computers are very much essential for generating,
managing and transmitting information.
Computers gain their importance at pharmaceutical company as
early as the 1940s.
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4. In 1940s – this is the era where the computers are only used for
accounting and payroll.
But, scientist accessed for computers , even though not present
in the company, then they accessed through contractual
agreement with other company.
Criteria for interest in the computer research,
a. Chemical structure is related to properties and its biological
activity.
b. Drug will exert biological activity by binding to inhibiting
some molecules.
c. Theory of quantum mechanics in the 1920s.
d. Quantitative structure activity relationship.
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5. Computational chemistry: the beginnings at
lilly
This narrative was first presented at Don boyd’s third Central
Indiana computational Chemistry Christmas Lucheon
(CICCCL-3) on December 18,1997.
Lily company and computer:
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6. 1940
Slide rulers
Usually of
Monroe and
Friden models
1949
IBM-7O4 = 1
million us dollar.
Vaccum tube
machine – only
payroll and
inventories are
carried out
Then IBM-7O9
1950
IBM – 650
Rotating drum –
2000 registries.
After the IBM –
610 was brought
in the company
by business group
– punched paper
input, program
and out put
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7. IBM – 7O4
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9. IBM – 7O9
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10. IBM - 650
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12. IBM - 610
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14. This was the system which gave invention of the
Drude equation – optical rotary dispersion data containing the
comparison between optical rotation and wavelength.
Then the IBM 1620 was used in the 1960 by the
company, which contained reader type drives and punch cards.
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15. Then the company hired a person called Dr, Robert.B.Hermann
who know how to use the computer for determining the
structure using properties.
Then Allison and Robert tried to obtain for IBM –
7094.
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16. THE 1960s – THE GERMINATION
 In 1960 – the IBM- 7904 were used by crystallographers and
theoratical chemists.
 Support staffs operated the tape readers, card readers and
printers.
 Programs were written in FORTRAN.
 In 1962, Quantum Chemistry Program Exchange was born for
exchanging ideas of software.
 It was the main source for structural calculations.
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17.  Program had self estimating feeded operating system – we call
it generally as software was discovered named , ORTEP – Oak
Ridge Thermal Ellipsoid Program.
 Late 1960s give the concept of SAR by computers use.
 Many theories were tried to evolve by computers i.e.,
Huckel Theory
Parier - Parr - Pople theory
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18. As the quantum mechanics was the basis, in addition to
the quantum chemistry in this era gave rise to QSAR i.e., Here
the activity of a compound was assumed to be linear or
quadratic or higher function of molecular descriptors.
Further it gave rise to measure the tendancy of
substituent to withdraw or donate electron density in relation to
the rest of the molecule.
In this this 1960s, rather than lily Abott , Schering-
Plough and Upjohn were the others company who got
interested in computer based research.
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19. GAINING A FOOTHOLD : THE 1970s
After having footholds in the developmental area of
computer many companies quit due to the lack of management
of technical criterias, but lilly was stubborn to the goal.
 Here they hiring more and more theoratical chemists who were
expert in organic chemistry and computers.
 Prof.E.J.Corey at Harvard was successful in attempting for
computer aided synthesis planning
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20. In the era of this 1970s the computer system used are IBM 360
and IBM 370 series.
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22. At instances,
Lily used system IBM-3278 and Decwriter II were used by
computational chemisrty group.
The statistics program used was MINITAB.
.
The typical office was used is shown in the figure;
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24.  Software was still written primarily in FORTRAN usually was
the version of FORTRAN IV.
 Hence holding of QCPE was expanded.
 In this 1970s the most important achievement was MMI/MMPI
program by Prof.L.Allingson
It leads to
a. Improvement of chemical accuracy
b. physical quantum mechanics
c. Molecular chemistry
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25. Hence this was the foothold for chemistry of drug but not for
pharmaceutical formulations.
After in the middle of 70s questioning to many of
queries there was launching of two new computer based
resources viz.,
1. Cambridge Structural Database(CSD)
2. Protein Data Bank (PDB)
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26. GROWTH : THE 1980s
The decades of the 1980s was the era where modern
approaches were seen in the field of quantum chemistry,
molecular mechanics, molecular simulations, QSAR and
molecular graphics.
The era of growth starts with development of the VAX 11/780
computer by digital equipment corporation (DEC) in 1979.
It was superminicomputer and was departmental size.
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27. Developments:
1. Development of personal computers and disk operating
system
2. The Apple Macintosh appeared on the scene in 1984.(400 kb
floppy disks was there )
3. Improvement of floppy disks in 1988 i.e., double sided,
double density disk with the capacity of 1400 KB.
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28. Advancements:
There three advancements in the software which were the turning
point for the development of computers
1. Development of electronic mail – which helped
computational staff and working staff to communicate easily.
2. The second development was the CHEMDRAW which was
released first for the Mac in 1986 – this gave chemists the
ability to quickly create two-dimensional chemical diagrams.
These diagrams could be cut and pasted into reports, articles,
and patents.
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29. 3. The third advancement was the great success i.e., the
developments of technology of computer graphics or 3D
structures – helped to understand
a. significance of highest molecular orbital.
b. The octanol water coefficients of structures.
The five companies succeeded in managing the computer
application in the pharmacy i.e.,
1. Abott
2. Dupont
3. Lederle,
4. Merc,Rohm and Haas
5. Searle,Smithkline Beecham and Upjohn
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30. THE FRUITION – 1990s
This is the modernized era where every company was
handling and developing many strategies in the drug
developments by computers.
 Here cray strategy was started.
 CEO and manager was assigned for the works.
 Silicon grade inc. And CPU based work started.
 Customized programs were started in pharmaceutical research
i.e.,
SYBL, BIOSYM, CHARMm etc.,
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31.  In 1990,BIOCAD became popular.
 In 1991, Dr, Jan.K.Labanowski an employee of Ohio
supercomputer center at Columbus, Ohio – launched an
electronic bulletin board called the Computational Chemistry
List (CCL).
 In 1991, MDL launched software called ISIS (Integrated
Scientific Information System).
 They provided new tools for drug research where chemicals
name were stored in tabular forms
Late 90 was the era for RAM
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32. The following factors can’t be described in early 80s. But now
each factor have it’s several softwares to define in the
computers.
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33. In 1997, Lipkin’s rules of five was published – contains coded
operation which can be used in easy manner.
Usually in 80s the discovery was only drug ligand oriented
computer research was adopted, hence the name was CALD.
But now novel properties are also described hence the name is
CADD
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35. References:
 Computer applications in pharmaceutical
research and development by John son and Wileys
– 2006 edition
page no. 3-49
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