Orientation and dynamics of Cu²⁺ based DNA labels from force field parameterized MD elucidates the relationship between EPR distance constraints and DNA backbone distances.

ABSTRACT: Pulsed electron paramagnetic resonance (EPR) based distance measurements using the recently developed Cu2+-DPA label present a promising strategy for measuring DNA backbone distance constraints. Herein we develop force field parameters for Cu2+-DPA in order to understand the features of this label at an atomic level. We perform molecular dynamics (MD) simulations using the force field parameters of Cu2+-DPA on four different DNA duplexes. The distance between the Cu2+ centers, extracted from the 2 μs MD trajectories, agrees well with the experimental distance for all the duplexes. Further analyses of the trajectory provide insight into the orientation of the Cu2+-DPA inside the duplex that leads to such agreement with experiments. The MD results also illustrate the ability of the Cu2+-DPA

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC10521111 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature