TREATMENT OF ROTATIONAL ISOMERIC STATES .3. THE USE OF BIASING POTENTIALS

A technique is described to determine umbrella biasing potentials that can be used to enhance sampling of rotational isomeric states in mole cular simulations of polypeptides in water. The analytical biasing pot ential function are obtained through fitting of potentials of mean for ce obtained by thermodynamic integration simulations to a small number of functions used to describe dihedral torsion. The resulting dramati c increase in efficiency of sampling is illustrated by comparison of m olecular simulations of the alanine-dipeptide molecule in aqueous solu tion, with and without the use of the biasing potentials. The same bia sing potentials were used in simulations of the alanine-tripeptide and the alanine-heptapeptide in aqueous solution. Similar dramatic increa ses in sampling efficiency were observed for these simulations, when t he biasing potentials were applied, which suggests that these biasing potentials, although determined for the dipeptide, may be transferable to larger peptide chains. It is illustrated how the biasing potential s can be used in biasing potential annealing simulations, leading to r apid folding of peptide chains into aqueous solutions structures with low energy.