Educational qualifications:

B. Sc. Chemistry(Honours), Midnapore College (Vidyasagar University)

M. Sc. in Chemistry (IIT Kanpur)

Post M Sc. diploma in Bio-Science (Saha Institute of Nuclear Physics)

Ph D in Structural Biology (Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics)

Post-doctoral research: MBU, IISc, Bangalore with Prof. M. Vijayan & Math-Bio, DST Centre for Mathematical Biology, IISc with Prof. Prabal K. Maiti

Course Manager, Vipassana: Vipassana Meditation & Research Centre, Dhamma Paphulla, Bengaluru.

Research Experiences:

Research synopsis: X-ray Crystallographic studies on Mycobacterial proteins: Pantothenate kinase and its complexes with substrates, products and inhibitor, Structural studies on Dps from Mycobacterium smegmatis, Structure-to-function correlation of a serine protease inhibitor protein, Chemical Crystallography, Homology Modelling & MD Simulation of ecto-domain of gp41 from HIV.

PhD work (at Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India):

Title of Ph. D. thesis: “Crystal Structure Analysis of a Trypsin / Chymotrypsin Inhibitor Protein from Psophocarpus tetragonolobus” .

(PhD degree awarded by Jadavpur University, Kolkata, West Bengal)

Protein-protein association is a common feature of all cellular functions. Proteinaceous inhibitors are ubiquitous in nature and formation of inactive hetero-complexes of proteinases and their respective proteinaceous inhibitors are used by nature to control proteinase activity. My doctoral work involved the crystal structure solution of a new STI-Kunitz type trypsin / chymotrypsin inhibitor protein (WCTI, Mw ~ 19.3 kDa) from winged bean (Psophocarpus tetragonolobus) seeds. Biochemical studies show that WCTI is capable of inhibiting beta-trypsin and alpha-chymotrypsin in the molar ratio 1:1, but the inhibition potency towards trypsin is much stronger than that towards chymotrypsin. Structural comparison with other inhibitor proteins, phylogenetic analysis, molecular dynamics simulation of its reactive site loop along with predictive docking studies with its cognate proteinases have been performed to rationalize it inhibition properties.

A template guided docking studies of WCTI with its target proteinases and their detailed analyses including multiple sequences alignment of the homologous sequences explains its biochemical properties and shades light on the inhibition properties of the other members of the family. Docking study includes optimization of crystallographic model, generation of enzyme-inhibitor docked models and then minimization by MULTIDOCK. The residue-residue interaction energy is more by 11.0 kcal / mol in the case of bet-trypsin complex, which supports the higher inhibition potency observed in biochemical studies. Interestingly, present predictive docking shows a “UP” conformation of the P₁ residue in the alpha-chymotrypsin complex. High-temperature (500 and 900 K) molecular dynamic simulations performed using DISCOVER_3 (Insight II Inc.) of the reactive site loop region confirmed its rigid-like nature, a characteristic feature of all the canonical serine proteinase inhibitor families.

I had also worked on the structure solution of a tetraphenylphosphonium salt of oxorhenium(V) cysteine complex. The rhenium chelate has been structurally correlated with the technetium chelates through comparable spectroscopic and chromatographic data. The technetium 99m analogue of this rhenium chelates exhibits renal tubular transport and renal retention, making this radiopharmaceuticals useful for evaluation of the clinical status of the renal patients.

Post-doctoral research experiences (IISc, Bangalore):

• Structural studies on mycobacterial proteins using x-ray crystallography (Two years as DBT-National PDF and three years as a Research Associate on Structural Genomics Project on Mycobaterium tuberculosis).

The gram-positive bacterium Mycobacterium tuberculosis (Mt) causes the infectious disease tuberculosis in humans. The complete genomic sequence of the best-characterized laboratory strain of Mt, H37Rv, is available. A worldwide effort is presently on to determine the structures of Mt proteins. During the post-doctoral tenure crystallization of several mycobacterial proteins was attempted which included enzymes involved in DNA manipulation (topoisomerase I from Mycobacterium smegmatis), proteins in cofactor and vitamin biosynthesis and a DNA-binding protein from starved cells (Dps) involved in the protection of DNA. The structures of two mycobacterial proteins: Dps from M. smegmatis and pantothenate kinase from Mycobacterium tuberculosis (MtPanK) which is a potential drug target have been solved, analyzed to explain their structure-function relationships and the results were published.

Structural studies on Dps from Mycobacterium smegmatis:

Dps (DNA-binding protein from starved cells) involved in protecting DNA from oxidative damage during nutritional deprivation. The Dps from M. smegmatis (MsDps) has 183 residues long polypeptide chain with molecular mass of 20.3 kDa. It posses ferroxidase and DNA binding activities. The structure of MsDps has been determined in three different crystal forms and has been compared with those of similar proteins from other sources. The subunits of MsDps molecule forms dodecameric assembly with 23 symmetry which can be described as a distorted icosahedron. The interfaces among subunits are such that the dodecameric molecule appears to have been made up of stable trimers. Structural analysis reveals that the trimerisation of MsDps is appears to be aided by the 11 residues long N-terminal stretch. It has an additional C-terminal stretch (26 residues) compared to other related proteins. This stretch, known to be involved in DNA binding, is situated on the surface of the molecule. The subunit interfaces around the molecular dyads, where the ferroxidation centers are located, are relatively rigid. Regions in the vicinity of the acidic holes centered around molecular 3-fold axes, are relatively flexible. The crystal structures of the protein from M. smegmatis confirm that DNA molecules can occupy spaces within the crystal without disturbing the arrangement of the protein molecules. However, contrary to earlier suggestions, the spaces do not need to be between layers of protein molecules. The cubic form provides an arrangement in which grooves, which could hold DNA molecules, criss-cross the crystal.

Structural analysis of pantothenate kinase from Mycobacterium tuberculosis (MtPanK): A kinetic crystallographic study for elucidation of the catalytic mechanism:

Pantothenate kinase (PanK) is a ubiquitous and essential enzyme that catalyzes the first step of the universal coenzyme A (CoA) biosynthetic pathway. In this step, pantothenate (vitamin B₅) is converted to 4'-phosphopantothenate, which subsequently forms CoA by four enzymatic steps. The PanK-catalyzed reaction is the rate-controlling step in CoA biosynthesis and is subjected to regulation by feedback inhibition by CoA and its thioesters. Although PanK occurs universally in living organisms, the sequence similarity between the prokaryotic and eukaryotic enzymes is very low. The non-availability of homologous PanK sequence in human enhances its value as a possible drug target. The defects in the PANK2 gene in humans are associated with neurodegenerative disorders, formerly known as Hallervorden-Spatz syndrome.

MtPanK is a homodimeric protein with subunit molecular weight of 35.7 kDa. It has been crystallized in complex with the coenzyme A in two different crystal forms and structure solved. The MtPanK subunit has a mononucleotide-binding fold with a seven-stranded central -sheet and helices on either side. The active-site pocket and the dimeric interface are on two opposite sides of the PanK subunit. A delineation of the invariant and variable features of the PanK structure indicates that the dimeric interface is very variable, while the coenzyme A-binding site is substantially invariant. A sequence alignment involving various bacterial PanKs is in agreement with this conclusion. The strong correlation between structural plasticity, evolutionary conservation and variability and function exhibited by the molecule could be important in the design of species-specific inhibitors of the enzyme.

Kinetic crystallographic strategy has been employed for the elucidation of catalytic mechanism of this enzyme. Several data set has been collected in complex with the substrates (pantothenate and ATP), products (4'-phosphopantothenate and ADP) and substrates analogues (pantothenol, N-nonyl pantothenamide and AMPPCP). We have demonstrated for first time the binding of substrates and products to any type I pantothenate kinase. The overall structure of the MtPanK remains similar to that of the coenzyme A complex. Structural analysis provided a wealth of information about the catalytic mechanism of the MtPanK in particular and type I pantothenate kinases in general.

Computational Structural Biology: Modelling & Simulation work on HIV-1 gp41 (Research Associate, Grade-III on Math-Bio DST project):

Molecular Mechanism of gp41 mediated HIV-1 entry to human cell: During my short post-doctoral tenure, I was involved in the investigations of the molecular mechanism of HIV-entry via cell-cell fusion and its inhibition using bio-computational techniques such as homology modeling and molecular dynamics simulation etc. Experimental evidence clearly established the involvement of gp41 in the fusion mechanism which undergoes major structural changes during cell-cell fusion. However, the molecular detail of structural change of gp41 and membrane rearrangements which leads to cell-cell fusion is not known. The non-availability of full-length ecto-domain gp41 structure was a hurdle for us. Initially we generated a homology model of full length HXB2 gp41 ecto-domain along with the trans-membrane region (1-194) in trimeric post-fusion conformation. Atomistic simulation indicated that overall three subunits exhibit asymmetric dynamic behaviour, likely indicating their differential functional role in the fusion process. It was a moot question, what would be the best possible simulation box in order to have reasonable molecular insight of gp41 mediated cell-cell fusion. Various possibilities of starting models using different conformation of gp41, lipid bi-layer model of human cell and HIV-1 were explored. Aim was to study the correlation of the gp41 conformational change and lipid bi-layer rearrangements which lead to successful cell-cell fusion by simulations and utilize the knowledge for inhibitor design.

Areas of Interest in Teaching

1. Engineering Chemistry

2. Scientific Foundations of Health

Areas of Interest in Research

Stucture-to-function correlation of biomolecules :

Macromolecular Crystallograhy

Computer aided structure based drug design

Molecular Dynamics Simulation

Biomineralization

Innovation & Entrepreneurship

Publications:

1. Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action. Chetnani, B.^#, Das, S.^#, Kumar, P., Surolia, A. and Vijayan, M. Acta Cryst. (2009). D65, 312 – 325. (^# both the authors contributed equally to this work). (eISSN: 1339-0047; Citations: 22; Impact factor: 7.652)

2. Invariance and variability in bacterial PanK: a study based on the crystal structure of Mycobacterium tuberculosis PanK. Das, S., Kumar, P., Bhor, V., Surolia, A. and Vijayan, M. Acta Cryst. (2006). D62, 628 – 38. (eISSN: 1339-0047; Citations: 48; Impact factor: 7.652)

3. X-ray analysis of Mycobacterium smegmatis Dps and a comparative study involving other Dps and Dps-like molecules. Roy, S., Gupta, S., Das, S., Sekar, K., Chatterji, D., Vijayan, M. J. Mol. Biol. (2004) 339, 1103 – 13. (ISSN: 0022-2836; Citations: 71; Impact factor: 5.469)

4. Oxorhenium(V) and Oxotechnetium(V) complexes of cysteine. Chatterjee, M., Achari, B., Das, S., Banerjee, R., Chakrabarti, C., Dattagupta, J. K. and Banerjee, S. Inorg. Chem. (1998) 37, 5424 – 5430. (ISSN: 0020-1669; Citations: 39; Impact factor: 5.165)

5. Specific recognition and Sensing of CN^- in Sodium Cyanide Solution. Saha, S., Ghosh, A., Mahato, P., Mishra, S., Mishra, S. K., Suresh, E., Das, S. and Das, A. Org. Lett. (2010) 12, 3406 – 3409. (ISSN: 1523-7060; Citations: 212, Impact factor: 6.005)

6. Expression, purification, crystallization and preliminary X-ray crystallographic analysis of pantothenate kinase from Mycobacterium tuberculosis. Das, S., Kumar, P., Bhor, V., Surolia, A. and Vijayan, M. Acta Cryst. (2005). F61, 65 – 67. (eISSN: 2053-230X; Citations: 11; Impact factor: 1.056)

7. Crystallization and preliminary X-ray diffraction analysis of Mycobacterium smegmatis Dps. Roy, S., Gupta, S., Das, S., Sekar, K,. Chatterji, D. and Vijayan, M. Acta Cryst. (2003) D59, 2254 – 6. (eISSN: 1339-0047; Citations: 09; Impact factor: 7.652)

8. Influence of chirality of V(V) Schiff base complexes on DNA, BSA binding and cleavage activity. Noor-ul H. Khan, Nirali Pandya, Nabin Ch. Maity, Manoj Kumar, Rajesh M. Patel, Rukhsana I. Kureshy, Sayed H. R. Abdi, Sandhya Mishra, Satyabrata Das, Hari C. Bajaj. Eur. J. Med. Chem. (2011) 46, 5074 – 85. (ISSN: 0223-5234; Citations: 57; Impact factor: 6.514)

9. Prediction and validation of HIV-1 gp41 ecto-transmembrane domain post-fusion trimeric structure using molecular modelling. Biswajit Gorai, Satyabrata Das and Prabal K. Maiti. J. of Biomolecular Structure & Dynamics (2020). 38(9), 2592-2603. (ISSN: 0739-1102; Citations: 01; Impact factor of 2020: 3.392)

10. Synthesis, structure elucidation and dft study of a new thiazole–pyridine anchored nnn donor and it's cobalt(II) complex: In-vitro antitumor activity against U937 cancer cells, dna binding property and molecular docking study. Pradip Bera, Abhishek Aher, Paula Brandao, Sunil Kumar Manna, Indranil Bhattacharyya, Chandana Pramanik, Basudev Mandal, Satyabrata Das and Pulakesh Bera. Journal of Molecular Structure (2021) 1224, 129015. (ISSN: 0022-2860; Citations: 03; Impact factor of 2020: 3.196)

PDB references: MtPanK, form I, room temperature, 2ges; low temperature, 2get; form II, room temperature, 2geu; low temperature, 2gev, initiation complex, 2zse; intermediate complex, 2zsf; end complex, 2zsa; citrate complex, 2zs7; complex with ADP and pantothenate, 2zs9; complex with CoA, 2zsd; complex with ADP (cocrystallized), 2zs8; complex with ADP (soaked), 2zsb.

Mycobacterium smegmatis DPS: 1VEI, 1VEL, 1VEQ

CCDC identifier: UMIXIY, UMIXEU, GATQAV .

Patent: Portable sprout making device (submitted)

Professional affiliation

Indian Crystallographic Association (ICA), India

Indian Biophysical Society (IBS), India

Distinctions

1. Qualified national level test (NET-1993) for the research fellowship and for the eligibility of lectureship in Chemical sciences, conducted jointly by Council of Scientific and Industrial Research (CSIR) and University Grant Commission (UGC), India

2. Qualified Graduate Aptitude Test in Engineering, GATE 1993 (percentile 99.27), India

3. Received merit-cum-means scholarship (1991-1993), Indian Institute of Technology Kanpur, Kanpur, India

4. Awarded University Silver Medal from Vidyasagar University for securing 2^nd rank in the B. Sc. (Hons.) examination in Chemistry of the year 1990

5. 1^st Prize in a departmental competition (Department of Chemistry, Midnapore College) on a topic “Unconventional Source of Energy” in the year 1989, in order to celebrate National Science Day, sponsored by Govt. of India

Events Attended

Poster presentations

1. Differential functional roles of subunits of gp41 trimer on HIV-entry: a study based on homology modeling and MD simulation. Satyabrata Das and Prabal K. Maiti, Math-Bio, DST-Centre for Mathematical Biology, Department of Physics, Indian Institute of Science, Bangalore – 560012, India at symposium “Molecules in Living Cells: Mechanistic basis of Function”, Annual Meeting of the Indian Biophysical Society, Organized by Indian Institute of Science Bangalore, February 8-10, 2016.

2. “Crystal structure and docking studies of a trypsin / chymotrypsin inhibitor protein from winged bean seeds”

Satyabrata Das, Rahul Banerjee, Kaustubh Datta, Rajamma Usha, Samir K. Datta, M. Singh and J. K. Dattagupta

37th National Seminar on Crystallography, February 6-8, 2008, organized by Department of Physics, Jadavpur University, Kolkata in collaboration with Indian Crystallographic Association and INSA National Committee for Crystallography

1. “Structural studies on pantothenate kinase from Mycobacterium tuberculosis in its apo form and binary and ternary complexes with its substrates, products and pantothenate analogues” Satyabrata Das, Bhaskar Chetnani, Parimal Kumar, A. Surolia and M. Vijayan. 11^th ADNAT Convention, A three-day Symposium on Advances in Structural Biology & Structure Prediction, Centre for Cellular and Molecular Biology, Hyderabad – 500 007, India, February 23-25, 2007.

2. “Structural studies on Mycobacterium tuberculosis PanK. Invariant nucleotide binding region and variable intersubunit interface”

Satyabrata Das, Parimal Kumar, Vikrant Bhor, A. Surolia and M. Vijayan National Symposium on Molecules, Interactions and Design: A Biophysical Perspective Under the aegis of Indian Biophysical Society, Jointly organized by West Bengal University of Technology and Saha Institute of Nuclear Physics, Kolkata, January 7-9, 2006.

1. “Structural studies on pantothenate kinase from Mycobacterium tuberculosis”

Satyabrata Das, Parimal Kumar, Vikrant Bhor, A. Surolia and M. Vijayan National Seminar on Crystallography (NSC34), Department of Chemistry, University of Guwahati, Assam, Gauhati, India, January 10-12, 2005.

1. “Crystallization of serine proteinase inhibitor (WCTI) from winged bean seeds”

Satyabrata Das, Rahul Banerjee and J. K. Dattagupta. XXVIIth National Seminar on Crystallography, Banaras Hindu University, Varanasi, February 28 - March 2, 1996.

Symposium / workshop attended

1. National Seminar on Crystallography (NSC33), National Chemical Laboratory, Pune – 411 008, India, January 8-10, 2004.

2. Golden Jubilee Symposium on Trends in Cellular and Molecular Biophysics, Saha Institute of Nuclear Physics, Kolkata, India, September 5-7, 2000.

3. Molecular Modeling Workshop, Departments of Biophysics Molecular Biology and Genetics, University of Calcutta, India, February 7-9, 2000.

4. International Seminar-cum-school on Macromolecular Crystallographic Data, Saha Institute of Nuclear Physics, Kolkata, India, November 16-20, 1995.

5. XVIth IUBMB Indian Satellite Symposium on Protein Structure Function and Engineering, Bose Institute, Kolkata, September 16-17, 1994.

6. FDP on "Scientific Foundations of Health", 9-11th May, 2022 organized jointly by VTU, Belagavi, Karnataka, India and Jyothy Institute of Technology, Bengaluru, Karnataka, India

Experience with XRD machines

v MAR300 / MAR345 image plate system mounted on Rigaku / Nonius rotating anode (CuK_a) and associated with Oxford cryosystem for the x-ray diffraction data collection of macromolecules.

v Bruker SMART APEX CCD area-detector diffractometer coupled with sealed tube x-ray generator (MoK_a) and Oxford cryosystem for the data acquisition of small molecule crystals

Programs used

Denzo, SCALEPACK and XDisplayF, AMoRe, PHASER, CCP4 package, CNS (v1.1), Insight II package (VIEWER, BUILDER, BIOPOLYMER and DISCOVER_3 module), PHYLIP, Multidock (v1.0), FRODO/O/COOT, NACESS, ALIGN, CLUSTALW, RASMOL, RIBBON, MOLSCRIPT, Raster 3D, BOBSCRIPT and ORTEP, SHELXL / SHELXS; MODELLER, GROMACS.

Programming knowledge Working experience with FORTRAN 77 / 90

Computer used SGI work station, PC (mainly LINUX), HPC Cluster, Cray XC40.