Hisstory of computers in pharmaceutical research and development

history of copmuters in pharmaceutical development and research

1. Presented by, Pratiksha C Chandragirivar M pharma 1 st sem Dept. of pharmaceutics HSK COP Bagalkot Facilitated to, Dr. Laxman Vijapur Assistant professor Dept. of pharmaceutics HSK COP Bagalkot cadd 1 History of computers in the pharmaceutical research and development

2. Contents: Introduction Computational chemistry : the beginnings at Lilly Germination:1960s Gaining the foothholds:1970s Growth :1980s The fruition : 1990s References cadd 2

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. cadd 3

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, Chemical structure is related to properties and its biological activity. Drug will exert biological activity by binding to inhibiting some molecules. Theory of quantum mechanics in the 1920s. Quantitative structure activity relationship. cadd 4

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: cadd 5

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7. IBM – 7O4 cadd 7

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9. IBM – 7O9 cadd 9

10. IBM - 650 cadd 10

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12. IBM - 610 cadd 12

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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. cadd 14

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. cadd 15

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. cadd 16

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 cadd 17

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. cadd 18

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 cadd 19

20. In the era of this 1970s the computer system used are IBM 360 and IBM 370 series. cadd 20

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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; cadd 22

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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 Improvement of chemical accuracy physical quantum mechanics Molecular chemistry cadd 24

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., Cambridge Structural Database(CSD) Protein Data Bank (PDB) cadd 25

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. cadd 26

27. Developments: Development of personal computers and disk operating system The Apple Macintosh appeared on the scene in 1984.(400 kb floppy disks was there ) Improvement of floppy disks in 1988 i.e., double sided, double density disk with the capacity of 1400 KB. cadd 27

28. Advancements: There three advancements in the software which were the turning point for the development of computers Development of electronic mail – which helped computational staff and working staff to communicate easily. 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. cadd 28

29. 3. The third advancement was the great success i.e., the developments of technology of computer graphics or 3D structures – helped to understand significance of highest molecular orbital. The octanol water coefficients of structures. The five companies succeeded in managing the computer application in the pharmacy i.e., Abott Dupont Lederle, Merc,Rohm and Haas Searle,Smithkline Beecham and Upjohn cadd 29

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., cadd 30

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 cadd 31

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. cadd 32

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 cadd 33

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35. References: Computer applications in pharmaceutical research and development by John son and Wileys – 2006 edition page no. 3-49 cadd 35

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