Dr. SHAKTI SAHI

Email :  ssahi@aib.amity.edu

Permanent Address: Shakti Sahi BHEL Township, Sector-17 NOIDA-201301 E-mail: ssahi@aib.amity.edu Phone: 0120-0000000 Mobile: 9911171897

Present Status

Working as Assistant Professor, Amity Institute of Biotechnology, Amity University, Sector-125, Noida.

Education

Ph.D. 1997-2002. Department of Biophysics, All India Institute of Medical Sciences (AIIMS), New Delhi, India

M.Pharm 1993-1995. Institute of Technology, B.H.U., Varanasi, India
Specialisation: Pharmaceutical Chemistry
Grade points: 9.36/10

B.Pharm 1989-1993. Institute of Technology, B.H.U., Varanasi, India.
Subjects: Pharmaceutical Sciences, Medicinal chemistry, Biochemistry, Pharmacognosy, Pharmacology, Mathematics.
Grade Points: 9.21/10

Employment

2003- 2007 Worked as Senior Lecturer, Bioinformatics, Amity Institute of Biotechnology, Noida

1995-1997 Worked as a Research Scientist in the Research and Development division of Panacea Biotech, New Delhi.

Job Profile

• Taking classes for various undergraduate and postgraduate courses at AIB in areas of Drug Design and development, Molecular modelling, Computational Biology, Proteomics, Pharmaceutical Chemistry, Pharma Management.
• Course coordinator for M.Sc (Bioinformatics) and B.Tech (bioinformatics) and also contribution in other courses of AIB.
• Arrangement of Guest lectures for Bioinformatics.
• Earlier responsible for students of PGD Bioinformatics and now M.Sc (Bioiinformatics) for summer training/placements in various institutes and industries for a period of 4-6 months.
• Established a Knowledge-alliance (MOU signed) with Mascon Life Sciences.
• Organised a 3-day National Workshop on Bioinformatics (September 2005). The workshop was inaugurated by Dr. T.Madhan Mohan, Director DBT..
• Developed the course for M.Sc (Bioinformatics), B.Tech (Bioinformatics) in consultation with experts from Industry/academia, contributed towards the development of M.Sc (Biotechnology), Integrated M.Tech (Biotech)course.
• Has been actively corresponding with CII regarding issues relating to strengthening of Bioinformatics sector in India.
• Submitted an HR-Mapping report on Biotech Sector in India as part of the survey being done by CII in collaboration with Amity
• Supervised project work of some students of M.Sc, B.Tech and B.Sc students

Computational Skills

• Proficient in working on Windows’95/98, Unix, Linux, and MS-DOS operating systems.
• Molecular modeling, Structure prediction and sequence analysis, homology modeling, molecular mechanics and dynamics. Proficient in usage of molecular modeling, analysis and graphics software packages like AMBER5.0, AMBER6.0, GCG, FLEXX, GRASP, MOLMOL, WEBLAB VIEWER, SWISSPDB, MOPAC, MS-CONOLLY, HYPERCHEM, SCHRODINGER, Molecular Operating Environment (MOE), MODEL (Molecular Modeling program) which is a general purpose, versatile molecular modeling package; includes geometry transformation and analysis, conformation and quantum chemical calculations; geometry analysis and graphics, IMF1 which is a grid based docking program and allows translational, rotational and conformational flexibility to ligand, as also conformational flexibility to side chains of the target. Originally written for UNIX; IMF1 is also available for LINUX and WINDOWS
• Knowledge of usage of Accelerys, Biosym, and data base management softwares like CDS/ISIS.
• Working Knowledge of HTML script writing
• Exposed to System administration in UNIX and LINUX platforms.

Wet Lab Skills

• Chemical Synthesis
• Pharmaceutical formulations
• Spectroscopy-UV, IR, NMR, Fluorescence Spectroscopy
• Chromatography techniques-Column, HPLC.
• Knowledge of Molecular biology techniques- ELISA

Major Workshops Attended/Organised

• Organised a workshop on Biocomputing techniques in collaboration with Mascon Life Sciences, September 2005.
• Indo-French WorkShop on Drug Design through Computational Approaches, 17th December,
2003, JNU, New Delhi.
• South -East Asian training course on Bioinformatics as Applied to tropical diseases, May 2002, International Center for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India.
• Workshop on Bioinformatics as applied to Parasitic diseases, January 2002, ICGEB New Delhi
• Summer school on Computer aided Drug design, June 1998, NIPER, Chandigarh

Awards/Fellowships/Acheivements

• AppointedHonorary Research coordinator for Bioinformatics in Eicosanoid & Lipid Research Division, University Medical Centre, Berlin since May 2006.
• Guest Faculty in Computer Science Department, Jamia-Milia Islamia University in year 2005-06, New Delhi
• April 2001-Jan. 2003: Research Associateship from Council of Scientific Industrial and Research (CSIR), New Delhi, India
• 1997-March 2001: Senior Research Fellowship from CSIR, New Delhi, India
• July 1993-April 1995: Junior Research Fellowship from UGC, India for qualifying in GATE, 1993.
• Prof. M. L. Schroff Award for Standing first all over India in B.Pharm.
• Gold medal from Banaras Hindu University, Varanasi for securing first rank in B.Pharm.

Research/Work Experience:

• Currently working on small molecules as potential anti diabetic and anticancerous agents.

• I visited Berlin, Germany for 1 month (May2006-June 2006) to participate in the International Conference on Non-mammalian eicosanoids and to carry out the collaborative research work between AIB and Eicosanoid and Lipid Research division, University Medical Centre Berlin Charité - Campus Benjamin Franklin. Formulated a project proposal which is submiited to Volkswagen Research Foundation in collaboration with Eicosanoid & Lipid Res. Div University Medical Centre Berlin Charité - Campus Benjamin Franklin, Berlin.

• Project Undertaken as Research Associate “Rational Designing of Cyclooxygenase-2/5-Lipoxygenase Inhibitors As Potential Anti-inflammatory Agents”
The aim of the present work is to design cyclooxygenase-2 and 5- lipoxygenase (COX-2/5-LOX) inhibitors as potential and safer antiinflammatory agents. Molecular modeling technique inclusive of molecular mechanics and molecular dynamics have been used for, firstly, determining the principles of recognition of active sites of COX-1 and COX-2 by different COX inhibitors and secondly, to design COX-2 selective inhibitors. The same techniques are being used to identify potential dual COX and LOX inhibitors.

• Project Undertaken in Ph.D. "Computational study of the mechanistic cause of differential activity of non-steroidal anti-inflammatory drugs and design of peptides and peptidomimetics as cyclooxygenase inhibitors (Molecular mechanics and Molecular dynamics study) under Dr. V. Kothekar, AIIMS.
Primary targets for NSAID's (non-steroidal anti-inflammatory drug) action is cyclooxygenase (COX) enzyme. This enzyme has two isoforms (COX-1 and COX-2). While COX-1 inhibition leads to serious gastrointestinal disorders, COX-2 inhibition is important for anti-inflammatory activity. Some of the currently known NSAIDs show differences in the selectivity of COX-1 and COX-2. Unfortunately, the amino acids in the active cavity, so also topology of the cavity is quite similar in COX-1 and COX-2. We studied transient structural changes in the active cavity, second shell amino acids and membrane binding domain induced by indoprofen (a nonspecific COX inhibitor), NS398 (a COX-2 selective inhibitor), benzofurans (having different selectivity and activity for COX), oxicams (currently a very popular group of NSAIDs), using computer modeling technique. A model for design of an inhibitor having selectivity for COX-2 is evolved. We designed several peptides and peptidomimetics which can selectively inhibit COX-2. The objective here was to identify the scaffold and modify it later for having higher selectivity for COX-2 and high potency. We used two strategies viz. cyclisation of peptides and introduction of constrained amino acid- ,  dehydro phenylalanine (Phe) in the peptide sequence. The conformational flexibility of the peptides was studied using systematic search and SAMD technique. Few of the low energy conformations were selected and docked into the active site of COX-1 and COX-2 using graphics package MOLMOL and grid based energy program IMF1. The complexes were energy minimsed and molecular dynamics carried out for 500 ps using Sander’s module of AMBER 5.0 on a Indigo II workstation. From the twelve peptides studied here we selected two peptides Pept-D1 and Pept-C2, on the basis of their interaction energy with COX-2 and COX-1 and points of contact with the enzyme (COX-2 and COX-1), for detailed evaluation of geometry based parameters. Both these peptides had a stable scaffold in free state as well as bound state. Four complexes Pept-D1-COX-2, Pept-D1-COX-1, Pept-C2-COX-2 and Pept-C2-COX-1 were energy minimised further and studied by molecular dynamics simulation technique. On the basis of these results we propose that both Pept-D1 and Pept-C2 could be COX-2 selective and potent inhibitors. Pept-D1 could be a better inhibitor because its backbone conformation was more stable; it made number of specific contacts with COX-2 and led to lesser distortion in overall geometry of the enzyme. It can act as a lead compound for design of COX-2 selective inhibitors. These results were corroborated by initial experimental assays using Cayman COX assay kit.
The various modelling and graphics packages used in this study included: AMBER 5.0 and AMBER 6.0, FLEXX, MOLMOL, RASMOL, LIGPLOT, PCURVE, GRASP, SWISSPDB, WEBLAB VIEWER, MOPAC, CNINDO, various structure prediction programs and in house programs like IMF1, MODEL, CONTACT etc.

• Project in Collaboration with Eicosanoid Research Division, Univ. Klinikum, Free University, Berlin, GERMANY, 2001.
As part of the project undergoing in the above mentioned group, I carried out molecular modeling studies on 3-R- and 3-S- HETE (3-hydroxy-5,8,11,14-eicosatetraenoic acid), which are metabolites of arachidonic acid (AA) carrying a hydroxyl group at C-3 position. These are found in a South African yeast Dipodascopsis uninucleata UOFS-Y128. The major isomer produced by the yeast is 3 (R)-HETE. These molecules are stereochemically identical to AA except that they carry an OH group at C-3 position. Recent experiments with COX-1, COX-2 and LOXs and their mutants showed (Nigam, S. personal communication) that 3R- and 3S-HETE can be transformed to corresponding 3-OH-eicosanoids. However, the activity of COX-2 was significantly reduced.

• Research Scientist in Panacea Biotech Ltd.,
I was working on the anti-inflammatory and cardiovascular compounds. My work involved the designing of strategy and carrying out the synthesis of few of these biologically active compounds and also scaling them from lab scale to pilot plant scale.

List of Publications:

1. In Silico Identification of Antioxidant gene G6PD in Caenorhabditiselegans
Jitendra N, Prachi S, Alpana V, Shakti S (2007) 8 (1) : 61-74, 2007 Online Journal of Bioinformatics, Australia

2. Oxygenation by cyclooxygenase-2 (COX-2) of 3-Hydroxyeicosa-tertraenoic acid (3-HETE), a fungal mimetic of arachidonic acid, produces a cascade of novel bioactive 3-hydroxyeicosanoids Roberto Ciccoli, Shakti Sahi, Sandhya Singh, Hridayesh Prakash, Maria-Patapia Zafiriou, Ganchimeg Ishdorj, Johan L.F. Kock, Santosh Nigam (2005) Biochem J. Sep 15;390(Pt 3):737-47

3. Kothekar, V., S. Sahi and M.Srinivasan (1999)"Computer Simulation of the interaction of non-steroidal anti-inflammatory drugs:Indoprofen and NS398 with cyclooxygenase" , J. Biomolecular Structure & Dynamics 16,4,901-915.

4. Sahi, Shakti., Srinivasan,M. and Kothekar, V (1999) , " 530 ps Molecular dynamics simulation of NSAIDs with COX-1 and COX-2. Study of purturbative changes", J.Molecular structure (Theochem) 498, 133-138.

5. Kothekar,V., Sahi, Shakti and Mishra Jyoti (2000) "Enzyme selectivity of new cyclooxygenase –2/5 lipoxygenase inhibitors using molecular modeling approach”, Indian J.Biochemistry and Biophysics, 37, 86-96

6. Kothekar, V., Sahi, S., Srinivasan, M., Mohan, A. and Mishra J. (2001) “
Recognition of cyclooxygenase-2 (COX-2) active site by NSAIDs: a computer modelling study” Indian J.Biochemistry and Biophysics, 38, 56-63 .

7. Kothekar, V., Sahi, S and Mishra, J (2001),” Molecular dynamics simulation of interaction of 5 keto substituted 7 tert Butyl 2,3 dihydrp, 3,3 dinethyl furan derivatives with cyclooxygenase -2”, Current Science, 80, 764-769.

8. Kothekar, V. and Sahi, S (2002) “Design of peptides and peptidomimetics as COX-2 selective inhibitors” J.Molecular Structure (Theochem),577,107-120.

List of conference Presentations

1. Kothekar, V. Sahi, Shakti., Srinivasan, M.Mohan Alok and Mishra Jyoti,” (Sept.1999) Recognition of cyclooxygenase active cavity by NSAIDs: Computer Modeling study”. Satellite symposium of XIIIth International Biophysics congress on structural Biology and Molecular Recognition, Calcutta,India, Invited Talk.

2. Kothekar, V. Sahi, Shakti and Srinivasan, M. (1999),” Structural basis of inhibition of integrase activity by ligands. A computer modelling study”, XIIIth International Biophysics congress, Delhi, India. J.Biosciences24,74-74.

3. Kothekar, V. Sahi, Shakti and Srinivasan, M.( 1999),” Molecular dynamics study of ligand induced purturbative changes in cyclooxygenase-I and 2”, XIIIth International Biophysics congress, Delhi, India. J.Biosciences24,50-50.

4. Kothekar, V. Sahi, Shakti and Mishra Jyoti (1999),” Study of the enzyme selectivity of new cyclooxygenase –2/5 lipoxygenase inhibitors using molecular modeling approach”,XIIIth International Biophysics congress, Delhi, India.

5. Kothekar, V. and Sahi, S. (2000) ”Design of peptides and peptidomimetics as cyclooxygenase (COX) inhibitors” National Symposium on Magnetic resonance and Biomolecular structure and Function, Bombay, India .

6. Kothekar,V. and Sahi,S. (2001) "Computational study of structure based ligand design" 71st Annual meeting of Indian Academy of Sciences, Pune, India . The paper was awarded a best research presentation award.

7. Shakti Sahi and Kothear, V. (2002) “Design of peptides and peptidomimetics as COX-2 selective inhibitors” International Symposium on Recent BioMedical Advances in Eicosanoid Research”, Berlin, GERMANY.

8. Shakti Sahi, Kothekar, V and Nigam, S. (2002)” Molecular Modeling studies of interaction of HETE with COX-1 and COX-2” International Symposium on Recent BioMedical Advances in Eicosanoid Research”, Berlin, GERMANY.

9. Roberto Ciccoli, Rupal Deva, Shakti Sahi, Lodewyk Kock, Santosh Nigam (Rome, Italy; Berlin, Germany; New Delhi, India; Bloemfontein, South Africa)
Conversion by fungi Dipodascopsis uninucleata of AA to 3-Hydroxy-eicosatetraenoic acid (3-HETE), a novel potent bioactive mimetic of AA, involves ß-oxidation associated multifunctional enzyme-2 (MFE-2) International Symposium on Non-mammalian Eicosanoids, Berlin (2006)

10. Roberto Ciccoli, Shakti Sahi, Rupal Deva, Lodewyk Kock, Santosh Nigam (Rome, Italy; Berlin, Germany; New Delhi, India; Bloemfontein, South Africa)
Oxygenation by COX-2 and 5-, 12- and 15-lipoxygenases of 3-hydroxy-eicosatetraenoic acid, a fungal mimetic of AA, produces a cascae of novel bioactive 3-hydroxy-eicosanoids. International Symposium on Non-mammalian Eicosanoids, Berlin (2006)

11. Roberto Ciccoli, Rupal Deva, Shakti Sahi, Lodewyk Kock, Santosh Nigam (Rome, Italy; Berlin, Germany; New Delhi, India; Bloemfontein, South Africa)
Conversion by fungi Dipodascopsis uninucleata of AA to 3-Hydroxy-eicosatetraenoic acid (3-HETE), a novel potent bioactive mimetic of AA, involves ß-oxidation associated multifunctional enzyme-2 (MFE-2) International Symposium on Non-mammalian Eicosanoids, Berlin (2006)

12. Santosh Nigam, Rupal Deva, Maren Lohse, Julia Dewitz, Aynur Baran, Ganchimeg Ishdorj, Roberto Ciccoli, Shakti Sahi, Lodewyk Kock, Anna Wesell and Hennie Cronjé (Berlin, Germany; New Delhi, India; Rome, Italy; Bloemfontein, South Africa)
Azole drug treatment is insufficient for therapy of recurrent vulvovaginal candidiasis: activation of COX-2 gene and production of novel bioactive arachidonic acid metabolites by C. albicans require novel therapy approach International Symposium on Non-mammalian Eicosanoids, Berlin (2006)

13. Shakti Sahi, Vidya Kothekar, Roberto Ciccoli, Lodewyk Kock, Santosh Nigam (New Delhi, India; Rome, Italy; Bloemfontein, South Africa; Berlin, Germany)
Conformational analysis of the interaction of 3-hydroxy-eicosatetraenoic acid (3-HETE), a novel fungal mimetic of AA, with cyclooxygenases ½ International Symposium on Non-mammalian Eicosanoids, Berlin (2006)