Structure-mechanics statistical learning unravels the linkage between local rigidity and global flexibility in nucleic acids.

Chemical Science
Yi-Tsao ChenJhih-Wei Chu

Abstract

The mechanical properties of nucleic acids underlie biological processes ranging from genome packaging to gene expression, but tracing their molecular origin has been difficult due to the structural and chemical complexity. We posit that concepts from machine learning can help to tackle this long-standing challenge. Here, we demonstrate the feasibility and advantage of this strategy through developing a structure-mechanics statistical learning scheme to elucidate how local rigidity in double-stranded (ds)DNA and dsRNA may lead to their global flexibility in bend, stretch, and twist. Specifically, the mechanical parameters in a heavy-atom elastic network model are computed from the trajectory data of all-atom molecular dynamics simulation. The results show that the inter-atomic springs for backbone and ribose puckering in dsRNA are stronger than those in dsDNA, but are similar in strengths for base-stacking and base-pairing. Our analysis shows that the experimental observation of dsDNA being easier to bend but harder to stretch than dsRNA comes mostly from the respective B- and A-form topologies. The computationally resolved composition of local rigidity indicates that the flexibility of both nucleic acids is mostly due to base-...Continue Reading

References

Jan 1, 1992·Annual Review of Biochemistry·R Schleif
Jun 1, 1990·Journal of Biomolecular Structure & Dynamics·M A Livshits Lyubchenko YuL
Mar 8, 1990·Nature·B S Fujimoto, J M Schurr
Oct 5, 1989·Journal of Molecular Biology·A C Dock-BregeonD Moras
Jan 1, 1988·Annual Review of Biophysics and Biophysical Chemistry·P J Hagerman
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·H R DrewR E Dickerson
Jan 1, 1997·Annual Review of Biophysics and Biomolecular Structure·P J Hagerman
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·W K OlsonV B Zhurkin
Jun 3, 2000·Journal of Molecular Biology·F LankasJ Langowski
Feb 13, 2001·Biophysical Journal·A R AtilganI Bahar
Jan 24, 2003·Nature·Carlos BustamanteSteven B Smith
Jul 18, 2003·Nature·Zev BryantCarlos Bustamante
Oct 29, 2003·Biophysical Journal·Filip LankasThomas E Cheatham
Jul 6, 2004·Nature Structural & Molecular Biology·Adam B ConwayPhoebe A Rice
Oct 7, 2004·Journal of Molecular Biology·Agnes NoyModesto Orozco
Nov 25, 2004·Nucleic Acids Research·Alberto PérezModesto Orozco
Feb 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·T E Cloutier, J Widom
Dec 20, 2005·Biophysical Journal·Jhih-Wei Chu, Gregory A Voth
Jul 25, 2006·Nature·Jeff GoreCarlos Bustamante
Aug 29, 2006·Nucleic Acids Research·Timothée LionnetVincent Croquette
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Nicholas R CozzarelliJames E Stray
Jan 17, 2008·The Journal of Physical Chemistry. B·U Deva Priyakumar, Alexander D Mackerell
Mar 1, 2008·Annual Review of Biochemistry·Jeffrey R MoffittCarlos Bustamante
Apr 22, 2008·ACS Chemical Biology·Jonathan B Chaires
Jul 26, 2008·Nature Nanotechnology·Paul A WigginsPhilip C Nelson
Mar 17, 2009·Science·Stephen C J ParkerElliott H Margulies
Jun 10, 2009·Physical Chemistry Chemical Physics : PCCP·Maxim Y Sheinin, Michelle D Wang
Sep 2, 2009·Biophysical Journal·Alexander J MastroianniA Paul Alivisatos
Mar 26, 2010·Annual Review of Biochemistry·Remo RohsRichard S Mann
May 19, 2010·Quarterly Reviews of Biophysics·Justin P Peters, L James Maher
Aug 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Stephanie Geggier, Alexander Vologodskii
Sep 23, 2010·Biophysical Journal·Ignacio FaustinoModesto Orozco
Nov 26, 2010·Nature Nanotechnology·Peixuan Guo
Mar 29, 2011·Current Opinion in Structural Biology·Stephen C J Parker, Thomas D Tullius
Jul 22, 2011·Nucleic Acids Research·Philip M D SeverinKlaus Schulten
Mar 1, 2012·Journal of Chemical Theory and Computation·Katarina HartAlexander D Mackerell
Mar 27, 2012·Annual Review of Biophysics·Iwijn De Vlaminck, Cees Dekker
Dec 12, 2012·Journal of the American Chemical Society·Elías Herrero-GalánJ Ricardo Arias-Gonzalez
Feb 15, 2013·The Journal of Chemical Physics·O GonzalezJ H Maddocks
Feb 16, 2013·Science·Sangjin KimX Sunney Xie
May 17, 2013·Nucleic Acids Research·Alexander Vologodskii, Maxim D Frank-Kamenetskii
Sep 10, 2013·Nucleic Acids Research·Justin P PetersL James Maher

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
chemical

Software Mentioned

haENM
3DNA
GROMACS
Nucleic Acid Builder

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.