The multiple-minima problem in protein folding

Cornell University, Ithaca, New York 14853-1301, USA.

Abstract

The conformational energy surface of a polypeptide or protein has many local minima, and conventional energy minimization procedures reach only a local minimum (near the starting point of the optimization algorithm) instead of the global minimum (the multiple-minima problem). Several procedures have been developed to surmount this problem, the most promising of which are:

• (a)

  build up procedure,

• (b)

  optimization of electrostatics,

• (c)

  Monte Carlo plus minimization,

• (d)

  electrostatically driven Monte Carlo,

• (e)

  inclusion of distance restraints,

• (f)

  adaptive importance sampling Monte Carlo

• (g)

  relaxation of dimensionality,

• (h)

  pattern recognition, and

• (i)

  diffusion equation method.

These procedures have been applied to a variety of polypeptide structural problems, and the results of such computations will be presented. These include the computation of the structures of open-chain and cyclic peptides, fibrous proteins and globular proteins. Present efforts are being devoted to scaling up these procedures from small polypeptides to proteins, to try to compute the three-dimensional structure of a protein from its amino sequence.