mathematics
and
computer
science

LANS

LANS Publications

"Computing Conformational Free Energy by Deactivated Morphing"

S. Park, A. Y. Lau, and B. Roux

Preprint ANL/MCS-P1492-0408

Preprint Version: [pdf]

Despite the significant advances in free energy computations for biomolecules, there exists no general method to evaluate the free energy difference between two conformations of a macromolecule that differ significantly from each other. A crucial ingredient of such a method is the ability to find a path between different conformations that allows an efficient computation of free energy. The free energy difference is the same no matter what path is taken, but not all paths are equally practical. In this paper we introduce a method named ’deactivated morphing’ and apply it to two test systems: alanine dipeptide and decaalanine, both in explicit water. An important feature of this method is the (shameless) use of nonphysical paths, which makes the method robustly applicable to conformational changes of arbitrary complexity.