Harmonic Fourier beads method for studying rare events on rugged energy surfaces.
We present a robust, distributable method for computing minimum free energy paths of large molecular systems with rugged energy landscapes. The method, which we call harmonic Fourier beads (HFB), exploits the Fourier representation of a path in an appropriate coordinate space and proceeds iteratively by evolving a discrete set of harmonically restrained path points-beads-to generate positions for the next path. The HFB method does not require explicit knowledge of the free energy to locate the path. To compute the free energy profile along the final path we employ an umbrella sampling method in two generalized dimensions. The proposed HFB method is anticipated to aid the study of rare events in biomolecular systems. Its utility is demonstrated with an application to conformational isomerization of the alanine dipeptide in gas phase.
Khavrutskii
Ilja V
IV
Department of Molecular Biology, The Scripps Research Institute, TPC6, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ikhavru@scripps.edu
Arora
Karunesh
K
Brooks
Charles L
CL
D000409:Alanine / Q000737:chemistry*; D000465:Algorithms; D003198:Computer Simulation; D004151:Dipeptides / Q000737:chemistry*; D007536:Isomerism; D008968:Molecular Conformation; D013816:Thermodynamics
D004151:Dipeptides; D000409:Alanine