Design of rapidly folding protein .. like heteropolymer chains and their cell dynamics.

Abstract

Understanding the  mechanism  of  protein  folding  is  a  fundamental  problem  in  molecular  biology.  Key  issues  include the  prediction  of  three-dimensional protein structure  from  one-dimensional  sequence  information  arid  the  inverse  problem  of  designing sequences  that  fold  into  a  desired  three-dimensional  structure.  One  of  the  puzzles  of  the  dynamics  of  protein  folding  ,  called  the  Levinthal  paradox.  is  the  rapidity  with  which  a  polypeptide  chain  folds into  the  native  state,  even  though  an  exhaustive  search  is  ruled  out  due  to  the  enormous  number  of  all  possible  conformations,  More  generally,  the  dynamics  of  protein  folding  is one  of  the  class  of  minimization  of  a fitness  function  characterized  by  complex  structure  and  many  local  minima.

It  is  well  known  that  lattice  models,  in  spite  of  their  simplicity,  capture  many  of  tile  features  of  protein  folding.  Using  the  computational facility at  SERC,  IISC,  we  have  designed  rapidly  folding  protein  like  heteropolymers  in  a  3-D  lattice. Secondly, the folding  pathway  is  elucidated  by  cell  dynamics  in  2-D  lattice.  The  details  of  these investigations  are  presented  in  this  paper.