Optimization of Parameters in Macromolecular Potential Energy Functions by Conformational Space Annealing
aw Pillardy,
Baker Laboratory of Chemistry and Chemical Biology, Cornell University,
Ithaca, New York 14853-1301, Program of Computational Sciences, Korea Institute
for Advanced Study, Seoul 130-012, Korea, Cornell Theory Center, Ithaca, New
York 14853-3801, and Faculty of Chemistry, University of Gda
sk,
Sobieskiego 18, 80-952 Gdask, Poland
Received: March 22, 2001
In Final Form: June 4, 2001
Abstract:
A general protocol for refining the parameters of macromolecular potential
energy functions by optimizing criteria that compare nativelike and nonnative
conformations of one or more benchmark protein(s) is described. The protocol
exploits the high efficiency of conformational space annealing (CSA) in finding
the lowest-energy conformation of an isolated macromolecule. A novel form of the
CSA method, local CSA, is introduced to provide better sampling of nativelike
conformations. The computational expense of the protocol is reduced
significantly by a linear approximation that estimates the energy of the (reminimized)
native and nonnative conformations after every change of the force field
parameters. The protocol is illustrated by optimizing the parameters of two
force fields used in the CASP3 and CASP4 experiments, respectively. Another
version of this general protocol (with different optimization criteria and
optimization methods) was used to determine the parameters for the 
,
and /
force fields used in the CASP4 experiment, as reported in a companion
publication (J. Pillardy et al. J. Phys. Chem. B 2001, 105,
7299).