Optimization of the CHARMM Additive Force Field for DNA: Improved Treatment of the BI/BII Conformational Equilibrium

Abstract

The B-form of DNA can populate two different backbone conformations: BI and BII, defined by the difference between the torsion angles ε and ζ (BI = ε-ζ < 0 and BII = ε-ζ > 0). BI is the most populated state, but the population of the BII state, which is sequence dependent, is significant and accumulating evidence shows that BII affects the overall structure of DNA, and thus influences protein-DNA recognition. This work presents a reparametrization of the CHARMM27 additive nucleic acid force field to increase the sampling of the BII form in MD simulations of DNA. In addition, minor modifications of sugar puckering were introduced to facilitate sampling of the A form of DNA under the appropriate environmental conditions. Parameter optimization was guided by quantum mechanical data on model compounds, followed by calculations on several DNA duplexes in the condensed phase. The selected optimized parameters were then validated against a number of DNA duplexes, with the most extensive tests performed on the EcoRI dodecamer, including comparative calculations using the Amber Parm99bsc0 force field. The new CHARMM model better reproduces experimentally observed sampling of the BII conformation, including sampling as a function of sequence. In addition, the model reproduces the A form of the 1ZF1 duplex in 75 % ethanol, and yields a stable Z-DNA conformation of duplex (GTACGTAC) in its crystal environment. The resulting model, in combination with a recent reoptimization of the CHARMM27 force field for RNA, will be referred to as CHARMM36.

In situ structure and dynamics of DNA origami determined through molecular dynamics simulations

“…All MD simulations reported in the main text were performed using the NAMD program (31), periodic boundary conditions, CHARMM36 force field for DNA (32), the modified TIP3P model of water (33), and custom parameters for ions (34). All Mg 2+ ions were simulated as Mg 2+ -hexahydrates (34).…”

A Coarse-Grained DNA Model Parameterized from Atomistic Simulations by Inverse Monte Carlo

“…The initial structure of the DNA double helix was built using the NAB package [67] with idealized B-DNA structure parameters. The simulation software was the Gromacs package [68,69] with the CHARMM27 force field [70,71] using the simple point charge model of water TIP3P [72][73][74]. The dimension of the cubic simulation cells was set to 90 Å.…”

Studying chemical reactions in biological systems with MBN Explorer: implementation of molecular mechanics with dynamical topology

“…The MM potential represents a phenomenological parametrization of the potential energy of a system and is widely used to describe structure and properties of macromolecular systems, such as polypeptides [43][44][45][46][47], proteins [47][48][49][50][51], DNA [32,[52][53][54], lipids [51,[55][56][57], and many others. All physically important interactions in a system, i.e.…”