Importance of long-time simulations for rare event sampling in zinc finger proteins

Abstract

Molecular dynamics (MD) simulation methods have seen significant improvement since their inception in the late 1950s. Constraints of simulation size and duration that once impeded the field have lessened with the advent of better algorithms, faster processors, and parallel computing. With newer techniques and hardware available, MD simulations of more biologically relevant timescales can now sample a broader range of conformational and dynamical changes including rare events. One concern in the literature has been under which circumstances it is sufficient to perform many shorter timescale simulations and under which circumstances fewer longer simulations are necessary. Herein, our simulations of the zinc finger NEMO (2JVX) using multiple simulations of length 15, 30, 1000, and 3000 ns are analyzed to provide clarity on this point.

Keywords:

• NEMO
• zinc finger
• molecular dynamics

Acknowledgments

Computations were, in part, performed on the Wake Forest University DEAC cluster. Thank you to Wake Forest Provost office and Information Systems Department for their support. Finally, thanks to Ryan Melvin for providing Matlab scripts for Markov analysis.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

FRS was partially supported by NIH [R01CA129373]; WFU Comprehensive Cancer Center [5P30CA012197-39]; and RCG was supported by SCB training [grant T32GM095440-04].