Alladi Ramakrishnan Hall

Chemical Dynamics in Biology

Prof. G. Krishnamoorthy

INSA Senior Scientist, Anna University, Chennai & Retired Senior Professor, Tata Institute of Fundamental Research, Mumbai

The complexity of biological world arises from the myriad of chemical structures and their associated dynamics. The wealth of structural information available in biology has led to the realization that a complete understanding of biological processes requires information on dynamics of the complex molecular systems apart from the knowledge on their high resolution structure. Despite this realization the level of information on dynamics is very scattered and highly insufficient.

A variety of physical techniques are being applied to bring out dynamic information on complex systems. Of these, fluorescence-based methods have a unique advantage due to their ultra-high sensitivity and selectivity. Furthermore, they cover a wide temporal range of femtosecond to seconds. In our laboratory we have been using various time-domain fluorescence techniques for addressing issues related to dynamics of proteins, protein-DNA complexes, biomembranes and single living cells. Subsequent to obtaining information on dynamics we then look for correlations between dynamics and biological function on these molecular systems. Such correlations, when established on firm grounds, bring out remarkable aspects of mechanistic details.

The following recent examples from our work will be described in detail for amplifying the above statements: (i) Motional dynamics of side chains were used to obtain structural information on partially-folded forms of proteins and early intermediates involved in protein folding; (ii)Time-evolution of structural change during folded-unfolded transition revealed by rotational dynamics was used to bring out the continuous nature of protein folding; (iii) Internal structure of protein fibrils was revealed by site-specific side-chain dynamics; (iv) Correlation between protein side-chain motion and solvent dynamics was established; (v) Local and segmental dynamics of DNA was used to reveal the mechanistic aspects in DNA recombination and DNA replication error identification and (vi) Site-specific dynamics was used in revealing the mechanism of action of an RNA switch.