Studying the Dynamics of a Complex G‑Quadruplex System: Insights into the Comparison of MD and NMR Data

Molecular dynamics
(MD) simulations are coming of age in the study
of nucleic acids, including specific tertiary structures such as G-quadruplexes.
While being precious for providing structural and dynamic information
inaccessible to experiments at the atomistic level of resolution,
MD simulations in this field may still be limited by several factors.
These include the force fields used, different models for ion parameters,
ionic strengths, and water models. We address various aspects of this
problem by analyzing and comparing microsecond-long atomistic simulations
of the G-quadruplex structure formed by the human immunodeficiency
virus long terminal repeat (HIV LTR)-III sequence for which nuclear
magnetic resonance (NMR) structures are available. The system is studied
in different conditions, systematically varying the ionic strengths,
ion numbers, and water models. We comparatively analyze the dynamic
behavior of the G-quadruplex motif in various conditions and assess
the ability of each simulation to satisfy the nuclear magnetic resonance
(NMR)-derived experimental constraints and structural parameters.
The conditions taking into account K+-ions to neutralize
the system charge, mimicking the intracellular ionic strength, and
using the four-atom water model are found to be the best in reproducing
the experimental NMR constraints and data. Our analysis also reveals
that in all of the simulated environments residues belonging to the
duplex moiety of HIV LTR-III exhibit the highest flexibility.