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Biography

Ramakrishna Vadrevu received his Masters degree in Physical Chemistry and his Ph.D. degree in Biophysical Chemistry.  He spent few years at the Pennyslvania State University and later at University of Massachusetts Medical School as a post doctoral fellow with Prof. C. Robert Mathews. Since 2008 he has been a faculty at the Birla Institute of Technology and Science-Pilani, Hyderabad Campus in the department of Biological Sciences.

His research focuses on understanding the role cellular environment on protein stability and folding. His research interests also include protein design and engineering, amyloid material and its applications. 

 

Abstract

Statement of the Problem: The acquired complex three-dimensional structure of proteins is a culmination of simple structural fragments like a-a, b-b, a-b and  b-a units.  Thus, tertiary structures can be seen as a combination of basic building block motifs implying that all complex protein structures have evolved from the assembly of small independently folding super secondary structures. The TIM barrel proteins are made up of a regular repeating bab motif resulting in the strands and helices in an alternating repetitive pattern. Experimental and theoretical studies have revealed that bab unit acts as a minimal unit of stability. The success of designing super secondary motifs that fold in isolation underscores the prospects of designing and or identification of independently folding motifs from the existing protein structures. However, intriguingly, naturally occurring bab sequences from proteins that fold independently have not been identified. In our attempts we addressed the finding of ‘needles in hay stick’ scenario by an exhaustive sequence and structural space search of the bab units                                                               from the TIM barrels.   Methodology & Theoretical Orientation: The search approach implemented in this work considered features such as alpha helical propensity, loop length, loop dynamics, residue preferences in loops, long range side chain main chain interactions etc., to shortlist bab units with strong propensity to fold in isolation.  The prospective bab candidates thus shortlisted from the TIM barrels have been further subjected to structure forming tendency employing a combination of Monte Carlo and Molecular dynamics simulations to assess their foldability and stability. Conclusion & Significance: The prediction of some independently folding bab candidates from TIMs are enabling us to experimentally asses their folding and stability. The identification and analysis of independently folding bab units that exist naturally will not only provide substantial information on nature’s design strategies and evolution of protein conformations but also help to design/engineer novel proteins

References:

  1. Grishin NV (2001). Fold change in evolution of protein structures. J Struct Biol. 134:167-85.
  2. Höcker B (2014). Design of proteins from smaller fragments-learning from evolution. Curr Opin Struct Biol. 27:56-62.
  3. Friedland GD, Kortemme T (2010). Designing ensembles in conformational and sequence space to characterize and engineer proteins. Curr Opin Struct Biol. 20:377-384.
  4. Riechmann L , Winter G (2006). Early protein evolution: building domains from ligand-binding polypeptide segments. J. Mol. Biol. 353:460-468
  5.   Yang X, Kathuria SV, Vadrevu R, Matthews CR. (2009). Beta alpha-  hairpin clamps brace beta alpha beta modules and can make substantive contributions to the stability of TIM barrel proteins. PLoS One. 4(9):e7179