We demonstrate the application of a biased Monte Carlo method for the optim
ization of protein sequences. The concept of configurational-biased Monte C
arlo has been used, but applied to sequence/composition rather than coordin
ates. Sequences of two-dimensional lattice proteins were optimized with the
new approach and results compared with conventional Monte Carlo and a self
-consistent mean-field (SCMF) method. Biased Monte Carlo (MC) was far more
efficient than conventional MC, especially on more complex systems and with
faster cooling rates. Biased MC did not converge as quickly as SCMF, but o
ften found better sequences. (C) 2000 American Institute of Physics. [S0021
-9606(00)51030-7].