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Structure-based Simulation of Riboswitches: Electrostatic Effects

基于结构的核糖开关模拟：静电效应

基本信息

批准号：
10612359
负责人：
Karissa Y Sanbonmatsu
金额：
$ 30.72万
依托单位：
TRIAD NATIONAL SECURITY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-15 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612359
关键词：
3-Dimensional Address Bacterial Genes Binding Biochemical Biochemistry Biological Assay Biological Models Biology Biophysics Biotechnology CRISPR/Cas technology Chemicals Clustered Regularly Interspaced Short Palindromic Repeats Collaborations Computational Technique Coupling Data Development Diffuse Electrostatics Elements Engineering Environment Event Gene Expression Regulation Genes Genetic Transcription Invaded Ion Exchange Ions Knowledge Length Ligand Binding Ligands Magnesium Maps Medicine MicroRNAs Modeling Molecular Molecular Conformation Physics Physiological Play Positioning Attribute Process Publishing RNA Role SAM Domain Sampling Small Interfering RNA Small RNA Solvents Structure System Techniques Technology Testing Titrations Training Transcript Work antimicrobial aptamer chelation experimental study flexibility magnesium ion molecular dynamics non-Native nucleotide analog operation simulation therapeutic development tool

项目摘要

Abstract With new developments in RNA biology, RNA biotechnology and RNA biomedicine each year, there is an urgent need to understand RNA mechanism in as much detail as possible. Small RNA techniques (miRNAs and siRNAs), and CRISPR-Cas9 gene editing are changing the landscape of biotechnology and biomedicine. Riboswitch RNAs are (i) important in bacterial gene regulation, (ii) interesting antimicrobial targets, and (iii) have potential for optimizing biotechnologies such as CRISPR-Cas9. These RNAs are excellent model systems for studying the hallmarks of RNA mechanism: magnesium-driven electrostatic effects, large 3-D conformational changes, changes in secondary structure, and co-transcriptional effects. Since 2009, we have published a variety of explicit solvent molecular dynamics simulation, structure-based molecular simulation, and wetlab biochemistry studies of riboswitches to understand their operation and the effect of magnesium on riboswitch structure and function. Focusing mainly on the aptamer domain of the SAM-I riboswitch, we have established that magnesium and SAM work together to achieve the fully collapsed, native state. In addition, magnesium facilitates a partial collapse, leaving the aptamer in a state permissible to strand invasion by the expression platform. In this project, we will study the entire riboswitch (aptamer and expression platform), investigating the role of magnesium in riboswitch function. Using atomistic structure-based electrostatic potential models for RNA and magnesium, we will disentangle the roles of inner sphere, outer sphere and diffuse magnesium ion effects in riboswitch operation. Using experimentally determined intermediate configurations, we will study transitions between intermediates during various points of riboswitch function. Our modeling we be enhanced by constraints from a variety of biochemical and biophysical experiments. We will address the fundamental question: How does the ionic environment enable riboswitch RNAs to accomplish their function?

摘要

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A magnesium-induced triplex pre-organizes the SAM-II riboswitch.

DOI：
10.1371/journal.pcbi.1005406
发表时间：
2017-03
期刊：
PLoS computational biology
影响因子：
4.3
作者：
Roy S;Lammert H;Hayes RL;Chen B;LeBlanc R;Dayie TK;Onuchic JN;Sanbonmatsu KY
通讯作者：
Sanbonmatsu KY

Chelated Magnesium Logic Gate Regulates Riboswitch Pseudoknot Formation.

DOI：
10.1021/acs.jpcb.1c02467
发表时间：
2021-06-24
期刊：
The journal of physical chemistry. B
影响因子：
0
作者：
Sarkar R;Jaiswar A;Hennelly SP;Onuchic JN;Sanbonmatsu KY;Roy S
通讯作者：
Roy S

Magnesium controls aptamer-expression platform switching in the SAM-I riboswitch.

镁控制 SAM-I 核糖开关中适体表达平台的切换。

DOI：
10.1093/nar/gky1311
发表时间：
2019
期刊：
Nucleic acids research
影响因子：
14.9
作者：
Roy,Susmita;Hennelly,ScottP;Lammert,Heiko;Onuchic,JoséN;Sanbonmatsu,KarissaY
通讯作者：
Sanbonmatsu,KarissaY

Tunable Riboregulator Switches for Post-transcriptional Control of Gene Expression.

DOI：
10.1021/acssynbio.5b00041
发表时间：
2015-12-18
期刊：
ACS synthetic biology
影响因子：
4.7
作者：
Krishnamurthy M;Hennelly SP;Dale T;Starkenburg SR;Martí-Arbona R;Fox DT;Twary SN;Sanbonmatsu KY;Unkefer CJ
通讯作者：
Unkefer CJ

Cooperation between Magnesium and Metabolite Controls Collapse of the SAM-I Riboswitch.

镁和代谢物之间的合作控制 SAM-I 核糖开关的崩溃。