Twenty-five years of nucleic acid simulations

Abstract

We present a brief, and largely personal, history of computer simulations of DNA and RNA oligonucleotides, with an emphasis on duplex structures and the Amber force fields. Both explicit and implicit solvent models are described, and methods for estimating structures, thermodynamics and mechanical properties of duplexes are illustrated. This overview, covering about two decades of work, provides a perspective for a discussion of prospects and obstacles for future simulations of RNA and DNA.

Keywords: force fields; molecular dynamics; nucleic acids.

Figure 1

Low-frequency—in and out of plane bending—modes of circular DNA. The arrows define the main motions associated with the corresponding vibration. Bending motions corresponding to n= 0 or n= 1 do not exist in the analytical model, so the first allowed bending comes for n= 2.

Figure 2

MM-PBSA analysis of the A to B form transition in d(CCAACGTTGG) ². Each column shows values for the B - A energy difference, in kcal/mol: a negative value (as for the total in red of −21.0 for DNA) indicates that the B helix is more stable than the A helix. Values are averages of 100 snapshots from each of four MD simulations (DNA and RNA, each in the A-form or B-form helix.) Values up to and including the red “total” line refer to zero added salt; values in the last two rows give “total” numbers for 0.1 M or 1.0 M added salt.