J. Chem. Phys. 110, 9730-9738 (1999).
A comparative study of existing and new design techniques for protein
Cristian Micheletti, Amos Maritan and Jayanth R. Banavar
Link to online article.
We present a detailed study of the performance and reliability of
design procedures based on energy minimization. The analysis is
carried out for model proteins where exact results can be obtained
through exhaustive enumeration. The efficiency of design techniques is
assessed as a function of protein length and the number of classes
into which amino acids are coarse grained. It turns out that, while
energy minimization strategies can identify correct solutions in most
circumstances, it may be impossible for numerical implementations of
design algorithms to meet the efficiency required to yield correct
solutions in realistic contexts. Alternative design strategies based
on an approximate treatment of the free energy are shown to be much
more efficient than energy-based methods while requiring nearly the
same CPU time. Finally, we present a novel iterative design strategy
that incorporates negative design with the use of selected decoy
structures that compete significantly with the target native state in
housing the designed sequences. This procedure allows one to identify
systematically all sequences that fold on a given target structure.