Refinement of RNA Structures Using Amber Force Fields.

David A. Case,Jonathon G. Gray

doi:10.3390/cryst11070771

David A. Case, Jonathon G. Gray

Open Access

https://doi.org/10.3390/cryst11070771

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Journal: Crystals	Publication Date: Jul 1, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Rutgers, The State University of New Jersey

Abstract

Atomic models for nucleic acids derived from X-ray diffraction data at low resolution provide much useful information, but the observed scattering intensities can be fit with models that can differ in structural detail. Tradtional geometric restraints favor models that have bond length and angle terms derived from small molecule crystal structures. Here we explore replacing these restraints with energy gradients derived from force fields, including recently developed integral equation models to account for the effects of water molecules and ions that are not part of the explicit model. We compare conventional and force-field based refinements for 22 RNA crystals, ranging in resolution from 1.1 to 3.6 Å. As expected, it can be important to account for solvent screening of charge–charge interactions, especially in the crowded environment of a nucleic acid crystal. The newly refined models can show improvements in torsion angles and hydrogen-bonding interactions, and can significantly reduce unfavorable atomic clashes, while maintaining or improving agreement with observed scattering intensities.

Highlights

RNA ribonucleic acid is involved in a wide variety of cellular processes, and atomic models describing their structures can be a key element in understanding their functions
The principal feature that differs between nucleic acids an proteins is the high charge density due to phosphate groups, and the need to describe the screening of such electrostatic interactions by water and ions that make up the bulk solvent
The results presented here illustrate choices that can be made at the final stages of crystallographic refinement, in an attempt to improve physical realisism of the final atomic model, while still maintaining the agreement with observed scattering factors

Summary

Introduction

RNA ribonucleic acid is involved in a wide variety of cellular processes, and atomic models describing their structures (often derived from X-ray diffraction studies) can be a key element in understanding their functions. In spite of the use of restraints on bond lengths and angles, there is a persistence of geometric outliers in RNA models developed from crystallographic data [1,2,3]. These outliers arise due to low resolution in many RNA structures [1,4], and due to the use of geometric restraints that do not consider the full range of electrostatic interactions and hydrogen-bonding terms that can be important for structural optimization [5]. Both authors have read and agreed to the published version of the manuscript

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Results

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