Repository logo
 

How accurate are accurate force-fields for B-DNA?

Published version
Peer-reviewed

Type

Article

Change log

Authors

Dans, Pablo D 
Ivani, Ivan 
Hospital, Adam 
Portella, Guillem 
González, Carlos 

Abstract

Last generation of force-fields are raising expectations on the quality of molecular dynamics (MD) simulations of DNA, as well as to the belief that theoretical models can substitute experimental ones in several cases. However these claims are based on limited benchmarks, where MD simulations have shown the ability to reproduce already existing 'experimental models', which in turn, have an unclear accuracy to represent DNA conformation in solution. In this work we explore the ability of different force-fields to predict the structure of two new B-DNA dodecamers, determined herein by means of 1H nuclear magnetic resonance (NMR). The study allowed us to check directly for experimental NMR observables on duplexes previously not solved, and also to assess the reliability of 'experimental structures'. We observed that technical details in the annealing procedures can induce non-negligible local changes in the final structures. We also found that while not all theoretical simulations are equally reliable, those obtained using last generation of AMBER force-fields (BSC1 and BSC0OL15) show predictive power in the multi-microsecond timescale and can be safely used to reproduce global structure of DNA duplexes and fine sequence-dependent details.

Description

Keywords

Base Sequence, Crystallography, X-Ray, DNA, B-Form, Molecular Dynamics Simulation, Nuclear Magnetic Resonance, Biomolecular, Nucleic Acid Conformation

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

45

Publisher

Oxford University Press (OUP)
Sponsorship
European Commission (654812)