When searching for an optimal protein structure, it is often necessary to
generate a set of structures similar, e.g., within 4A Root Mean Square
Deviation (RMSD), to some base structure. Current methods to do this are
designed to produce only small deviations (< 0.1A RMSD) and are ine1cient
for larger deviations. The method proposed in this paper, ChainTweak, can
generate conformations with larger deviations from the base much more
e1ciently. For example, in 18 seconds it can generate 100 backbone
conformations, each within 14:A RMSD of a given 45residue conformation.
Moreover, each conformation has correct bond lengths, angles and omega
torsional angles; and its phipsi angles have energetically favorable
values and there are rarely any backbone steric clashes. The method uses
the insight that loop closure techniques can be used to perform
compensatory changes of dihedral angles so that only a part of the
conformation is changed. It is demonstrated, using decoys from the Decoys
'R Us dataset, that ChainTweak can be used to construct good decoys. It
also provides a novel and intuitive way of analyzing the energy landscape
of a protein. In addition, ChainTweak can improve the accuracy and
performance of the loop modeling program RAPPER by an order of magnitude
(1.1 min vs. 36 min for an 8residue chain).
