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SUMMARY:The Evolutionary 'Design' of Proteins - Rama Ranganathan\, UT Sout
 hwestern Medical Centre
DTSTART:20130904T100000Z
DTEND:20130904T110000Z
UID:TALK46578@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Natural proteins can fold spontaneously into well-defined thre
 e-dimensional structures\, and can display complex biochemical properties 
 such as signal transmission\, efficient catalysis of chemical reactions\, 
 specificity in molecular recognition\, and allosteric conformational chang
 e.  All of this is achieved while also preserving the capacity for rapid a
 daptive variation in response to fluctuating selection pressures\, a centr
 al feature of evolving systems.  What are the basic principles in the “d
 esign” of natural proteins that underlie all of these properties?  To ad
 dress this\, we developed an approach (the statistical coupling analysis o
 r SCA) for globally estimating the pattern of functional interactions betw
 een sites on proteins through statistical analysis of the evolutionary div
 ergence of a protein family1\,2.  This analysis indicates a novel decompos
 ition of proteins into sparse groups of co-evolving amino acids that we te
 rm “protein sectors”9.  The sectors comprise physically connected netw
 orks in the tertiary structure and can be modular – with different secto
 rs representing different functional properties.  Experiments in several p
 rotein systems demonstrate the functional and adaptive importance of the s
 ectors 1\,3\,4\,7\,8\,10\,11\,12 and recently\, the SCA information was sh
 own to the necessary and sufficient to design functional artificial member
 s of two protein families in the absence of any structural or chemical inf
 ormation5\,6.  These results support the hypothesis that sectors represent
  the basic architecture underlying folding\, function\, and adaptive varia
 tion in proteins.  We are now working on two key problems: (1) understandi
 ng the physical mechanisms underlying sectors\, and (2) defining how the d
 ynamics of the evolutionary process controls the emergence and structural 
 architecture of sectors in proteins
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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