Education
Research Interests
Reports
Publications
  

Pratul K. Agarwal

Phone: (865) 574-7184
E-mail: agarwalpk_AT_ornl.gov
Staff Scientist
Computational Biology Institute &
Computer Science and Mathematics Division
Oak Ridge National Laboratory, Oak Ridge
 Adjunct Faculty
Graduate School in
Genome Science and Technology
University of Tennessee, Knoxville

Education:
Integrated M. Tech. (B. Tech. + M. Tech.) in Biochemical Engineering and Biotechnology (1997)

Indian Institute of Technology-Delhi, New Delhi, India

Ph.D. Theoretical Chemistry and Biochemistry (2002)

The Pennsylvania State University, University Park, PA 16802

Thesis title: Quantum Effects and Protein Motion in Enzymatic Catalysis

Thesis Advisor: Prof. Sharon Hammes-Schiffer


Professional Experience:
  • Post-doctoral Research Associate: Oak Ridge National Laboratory, Oak Ridge, TN
    (May 2002 - Apr 2005)
  • Staff Scientist: Computational Biology Institute & Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, TN
    (Apr 2005 - present)
  • Adjunct Faculty, Graduate program in Genome Science and Technology, University of Tennessee, Knoxville, TN
    (Jan 2006 - present)


    • Research Interests:
  • Multi-scale modeling to investigate protein folding, structure, dynamics and function:

    • It is widely discussed that computational modeling and simulations will play a critical role in next revolution in biology. We are interested in using large scale simulations to investigate various aspects of biomolecular structure, dynamics and function. Biological processes span multiple scales of time and length. In collaboration with experimental scientists (Dean A. Myles, Director of Center for Structural Molecular Biology, ORNL & William T. Heller, Chemical Sciences Division, ORNL), we are performing multi-scale modeling of various biomolecular complexes. Techniques including neutron scattering (Spallation Neutron Source and High Flux Isotope Reactor) and X-ray scattering will be used for investigating structural and dynamical properties of proteins.


    Cyclophilin A: Using multi-scale modeling, we have discovered a network of protein vibrations in the enzyme cyclophilin A, coupled to its catalytic activity of peptidyl-prolyl cis-trans isomerization.
    This network, extending from surface regions to the active-site, is conserved part of enzyme structure and has a role in promoting catalysis. Protein vibrations promote catalysis by altering transition barrier recrossings behavior of reaction trajectories. Cyclophilin A has medical implication, as it plays a role in infectious activity of human immunodeficiency virus type-1 (HIV-1).


    A network of vibrations promoting catalysis in enzyme cyclophilin A.

  • Optimization of biomolecular modeling code for high performance computing:

    • The available computing power for modeling and simulations falls short by several orders of magnitude in comparison of what is required to simulate events at biologically relevant time and length scales. Supercomputers such as IBM Blue Gene\L and Cray XT3 will soon make teraFLOP/s and petaFLOP/s of computing power available to the biologists. The popular MD codes, however, were not designed to run on many thousands of processors. In collaboration with Future Technologies Group (ORNL), issues crucial for improving the scalability of the MD codes on massively parallel architectures are being investigated. Detailed studies investigating the behavior of popular MD codes have been performed for network communication and memory fingerprinting using biomolecular complexes to identify the bottlenecks.


  • Designing new computational algorithms for scientific applications:

    • We are interested in designing novel computational algorithms to address the “Grand Challenge” problems in science. The current area of focus includes computational biology, chemistry and the interesting area “nano-info-bio”, which has very interesting implications.

  • Linux for scientific applications:

    • Developer of VigyaanCD, a bio/chemical software workbench. Based on Knoppix, VigyaanCD provides over 25 popular tools for bioinformatics and computational biology to the user without requiring separate installation of software. Since its launch more than 50,000 copies of the CD have been downloaded around the world.
    Contributor to BiLab. BiLab is an interactive environment for the bio-science community to aid in research in the areas of bioinformatics, computational biology and related domains.


    VigyaanCD
    BiLab

    Reports and Conference Proceedings:

    1. Protein Dynamics and Function: PITAC Report to the President on Computational Science: Ensuring America's Competitiveness. [Page 83, Page 97 of PDF file]
    2. Vibrations may be Key to Protein Functions: DOE Advanced Scientific Computing Research FY 2004 Accomplishment.
    3. Evaluation of the SGI Altix 3700 at Oak Ridge National Laboratory.
    4. Cray X1 Evaluation Status Report, Proceedings of the 46th Cray User Group Conference, Knoxville, TN, May 17-20, 2004.
    5. Alam, S. R.*, Agarwal, P. K.*, Vetter, J. S., Geist A., "Performance characterization of bio-molecular simulations using molecular dynamics", PPoPP 2006 Proceedings.
    6. Agarwal, P. K.*, Alam, S. R., "Biomolecular Simulations on Petascale: Promises and Challenges", Accepted. J. Physics (SciDAC 2006 Proceedings).
    7. Alam, S. R., Agarwal, P. K., Vetter, J. S., Smith, M., Caliga, D., "Acceleration of a Bio-molecular Simulation on Field Programmable Gate Arrays using High-Level Languages", Submitted: Supercomputing 2006 Proceedings.

    Journal Publications:
    (*indicates corresponding authorship) 

    1.  Agarwal, P. K.*, “Protein Dynamics Promoting Protein Function”, Invited Current Topics Article: Biochemistry  

    2.  Agarwal, P. K.*, “Conformational flexibility of proteins: Evolutionary linkage between protein fold, dynamics and function”, Submitted.  

    3.  Sosa, C. P, Agarwal, P.K., Alam, S. R., Smith, R., Case, D. A., Crowley, M.,“Molecular Dynamics Performance Analysis on the Massively Parallel Supercomputer Blue Gene/L: AMBER8”, Under review.

    4.  Agarwal, P. K.*, “ Enzymes: An integrated view of structure, dynamics and function ”, Invited Review Article: Microbial Cell Factories. (2006) 5:2.
    Evaluated by Faculty of 1000 Biology

    5.  Agarwal, P. K.*, “Role of Protein Dynamics in Reaction Rate Enhancement by Enzymes”, J. Am. Chem. Soc. (2005) 127, 15248-15246.  
    Evaluated by Faculty of 1000 Biology

    6.  Agarwal, P. K.*; Geist, A.; Gorin, A., “Protein Dynamics and Enzymatic Catalysis: Investigating the Peptidyl-Prolyl cis/trans Isomerization Activity of Cyclophilin A”, Biochemistry (2004) 43, 10605-10618.  

    7.  Agarwal, P. K.*, “Computational studies of the mechanism of cis/trans isomerization in HIV-1 catalyzed by cyclophilin A”, Proteins: Struct. Funct. Bioinformatics (2004) 56, 449-463. 

    8.  Watney, J. B.; Agarwal, P. K.; Hammes-Schiffer, S., “Effect of mutation on enzyme motion in dihydrofolate reductase”, J. Am. Chem. Soc. (2003) 125, 3745-3750.  

    9.  Agarwal, P.K.; Billeter, S.R.; Hammes-Schiffer, S., “Nuclear quantum effects and enzyme dynamics in dihydrofolate reductase catalysis”, J. Phys. Chem. B (2002) 106, 3283-3293. 

    10.  Agarwal, P.K.; Billeter, S.R.; Rajagopalan, P.T.R.; Benkovic, S.J.; Hammes-Schiffer, S., “Network of Coupled Promoting Motions in Enzyme Catalysis”, Proc. Natl. Acad. Sci. USA (2002) 99, 2794-2799.  
    Evaluated by Faculty of 1000 Biology

    11.  Billeter, S.R.; Webb, S.P.; Agarwal, P.K.; Iordanov, T.; Hammes-Schiffer, S., “Hydride Transfer in Liver Alcohol Dehydrogenase: Quantum Dynamics, Kinetic Isotope Effects, and the Role of Enzyme Motion”, J. Am. Chem. Soc. (2001) 123, 11262-11272. 

    12.  Billeter, S.R.; Webb, S.P.; Iordanov, T.; Agarwal, P.K.; Hammes-Schiffer, S., “Hybrid Approach for Including Electronic and Nuclear Quantum Effects in Molecular Dynamics Simulations of Hydrogen Transfer Reactions in Enzymes”, J. Chem. Phys. (2001) 114, 6925-6936.  

    13.  Webb, S.P.; Agarwal, P.K.; Hammes-Schiffer, S., “Combining Electronic Structure Methods with Calculation of Hydrogen Vibrational Wavefunctions: Application to Hydride Transfer Catalyzed by Liver Alcohol Dehydrogenase”, J. Phys. Chem. B (2000) 104, 8884-8894. 

    14.  Agarwal, P.K.; Webb, S.P.; Hammes-Schiffer, S., “Computational Studies of the Mechanism for Proton and Hydride Transfer in Liver Alcohol Dehydrogenase”, J. Am. Chem. Soc. (2000) 122, 4803-4812. 

    15.  Agarwal P.K.; Bhattacharya S.K., “Construction of a multi RE module: Exploitation of mechanochemistry of restriction endonucleases”, Biotechnology & Bioengineering (1999) 65, 233-239.   
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