Improved Force Field Parameters Lead to a Better Description of RNA Structure.

We compare the performance of two different RNA force fields in four water models in simulating the conformational ensembles r(GACC) and r(CCCC). With the increased sampling facilitated by multidimensional replica exchange molecular dynamics (M-REMD), populations are compared to NMR data to evaluate force field reliability. The combination of AMBER ff12 with vdW(bb) modifications and the OPC water model produces results in quantitative agreement with the NMR ensemble that have eluded us to date.

[1]  Duncan Poole,et al.  Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 1. Generalized Born , 2012, Journal of chemical theory and computation.

[2]  T. Straatsma,et al.  THE MISSING TERM IN EFFECTIVE PAIR POTENTIALS , 1987 .

[3]  Harry A. Stern,et al.  Reparameterization of RNA χ Torsion Parameters for the AMBER Force Field and Comparison to NMR Spectra for Cytidine and Uridine , 2010, Journal of chemical theory and computation.

[4]  J. Šponer,et al.  Refinement of the Cornell et al. Nucleic Acids Force Field Based on Reference Quantum Chemical Calculations of Glycosidic Torsion Profiles , 2011, Journal of chemical theory and computation.

[5]  Niel M. Henriksen,et al.  Reliable oligonucleotide conformational ensemble generation in explicit solvent for force field assessment using reservoir replica exchange molecular dynamics simulations. , 2013, The journal of physical chemistry. B.

[6]  T. Ichiye,et al.  Study of multipole contributions to the structure of water around ions in solution using the soft sticky dipole-quadrupole-octupole (SSDQO) model of water. , 2006, The Journal of chemical physics.

[7]  A. Roitberg,et al.  Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning. , 2015, Journal of chemical theory and computation.

[8]  Saeed Izadi,et al.  Building Water Models: A Different Approach , 2014, The journal of physical chemistry letters.

[9]  Niel M. Henriksen,et al.  Highly sampled tetranucleotide and tetraloop motifs enable evaluation of common RNA force fields , 2015, RNA.

[10]  L. Nilsson,et al.  Structure and Dynamics of the TIP3P, SPC, and SPC/E Water Models at 298 K , 2001 .

[11]  David A Case,et al.  Twenty-five years of nucleic acid simulations. , 2013, Biopolymers.

[12]  P. Kollman,et al.  How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? , 2000 .

[13]  D. Turner,et al.  Benchmarking AMBER Force Fields for RNA: Comparisons to NMR Spectra for Single-Stranded r(GACC) Are Improved by Revised χ Torsions , 2011, The journal of physical chemistry. B.

[14]  Andrew T. Fenley,et al.  Charge hydration asymmetry: the basic principle and how to use it to test and improve water models. , 2012, The journal of physical chemistry. B.

[15]  Pengfei Li,et al.  Rational Design of Particle Mesh Ewald Compatible Lennard-Jones Parameters for +2 Metal Cations in Explicit Solvent. , 2013, Journal of chemical theory and computation.

[16]  D. Case,et al.  Revised AMBER parameters for bioorganic phosphates. , 2012, Journal of chemical theory and computation.

[17]  K. Réblová,et al.  Understanding RNA Flexibility Using Explicit Solvent Simulations: The Ribosomal and Group I Intron Reverse Kink-Turn Motifs. , 2011, Journal of Chemical Theory and Computation.

[18]  P. Kollman,et al.  A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat. , 1999, Journal of biomolecular structure & dynamics.

[19]  Julian Tirado-Rives,et al.  Potential energy functions for atomic-level simulations of water and organic and biomolecular systems. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Duncan Poole,et al.  Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh Ewald. , 2013, Journal of chemical theory and computation.

[21]  T. Cheatham,et al.  Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations , 2008, The journal of physical chemistry. B.

[22]  J. Šponer,et al.  Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers , 2007 .

[23]  Greg L. Hura,et al.  Development of an improved four-site water model for biomolecular simulations: TIP4P-Ew. , 2004, The Journal of chemical physics.

[24]  Adrian E. Roitberg,et al.  Multidimensional Replica Exchange Molecular Dynamics Yields a Converged Ensemble of an RNA Tetranucleotide , 2013, Journal of chemical theory and computation.

[25]  Angel E García,et al.  High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations , 2013, Proceedings of the National Academy of Sciences.

[26]  D. Turner,et al.  The Nuclear Magnetic Resonance of CCCC RNA Reveals a Right-Handed Helix, and Revised Parameters for AMBER Force Field Torsions Improve Structural Predictions from Molecular Dynamics , 2013, Biochemistry.