Exploring Conformational
Landscapes Along Anharmonic
Low-Frequency Vibrations
Posted on 2024-07-10 - 20:10
We aim to automatize the identification of collective
variables
to simplify and speed up enhanced sampling simulations of conformational
dynamics in biomolecules. We focus on anharmonic low-frequency vibrations
that exhibit fluctuations on time scales faster than conformational
transitions but describe a path of least resistance toward structural
change. A key challenge is that harmonic approximations are ill-suited
to characterize these vibrations, which are observed at far-infrared
frequencies and are easily excited by thermal collisions at room temperature.
Here, we approached this problem with a frequency-selective anharmonic
(FRESEAN) mode analysis that does not rely on harmonic approximations
and successfully isolates anharmonic low-frequency vibrations from
short molecular dynamics simulation trajectories. We applied FRESEAN
mode analysis to simulations of alanine dipeptide, a common test system
for enhanced sampling simulation protocols, and compared the performance
of isolated low-frequency vibrations to conventional user-defined
collective variables (here backbone dihedral angles) in enhanced sampling
simulations. The comparison shows that enhanced sampling along anharmonic
low-frequency vibrations not only reproduces known conformational
dynamics but can even further improve the sampling of slow transitions
compared to user-defined collective variables. Notably, free energy
surfaces spanned by low-frequency anharmonic vibrational modes exhibit
lower barriers associated with conformational transitions relative
to representations in backbone dihedral space. We thus conclude that
anharmonic low-frequency vibrations provide a promising path for highly
effective and fully automated enhanced sampling simulations of conformational
dynamics in biomolecules.
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Mondal, Souvik; Sauer, Michael A.; Heyden, Matthias (2024). Exploring Conformational
Landscapes Along Anharmonic
Low-Frequency Vibrations. ACS Publications. Collection. https://doi.org/10.1021/acs.jpcb.4c02743