K. Tappura, Influence of rotational energy barriers to the conformational search of protein loops in molecular dynamics and ranking the conformations, PROTEINS, 44(3), 2001, pp. 167-179
An adjustable-barrier dihedral angle potential was added as an extension to
a novel, previously presented soft-core potential to study its contributio
n to the effectivity of the search of the conformational space in molecular
dynamics. As opposed to the conventional soft-core potential functions, th
e leading principle in the design of the new soft-core potential, as well a
s of its extension, the soft-core and adjustable-barrier dihedral angle (SC
ADA) potential (referred as the SCADA potential), was to maintain the main
equilibrium properties of the original force field. This qualifies the meth
ods for a variety of a priori modeling problems without need for additional
restraints typically required with the conventional soft-core potentials.
In the present study, the different potential energy functions are applied
to the problem of predicting loop conformations in proteins. Comparison of
the performance of the soft-core and SCADA potential showed that the main h
urdles for the efficient sampling of the conformational space of (loops in)
proteins are related to the high-energy barriers caused by the Lennard-Jon
es and Coulombic energy terms, and not to the rotational barriers, although
the conformational search can be further enhanced by lowering the rotation
al barriers of the dihedral angles. Finally, different evaluation methods w
ere studied and a few promising criteria found to distinguish the near-nati
ve loop conformations from the wrong ones. (C) 2001 Wiley-Liss, Inc.