RNA unwinding from reweighted pulling simulations

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The forming and melting of complementary base pairs in RNA duplexes are conformational transitions required to accomplish a plethora of biological functions. Yet the dynamic steps of these transitions have not been quantitatively characterized at the molecular level. In this work, the base opening process was first enforced by atomistic pulling simulations and then analyzed with a novel reweighting scheme which allowed the free-energy profile along any suitable reaction coordinate, e.g. solvation, to be reconstructed. The systematic application of such approach to different base-pair combinations provides a molecular motion picture of helix opening which is validated by comparison with an extensive set of experimental observations and links them to the enzyme-dependent unwinding mechanism. The RNA intrinsic dynamics disclosed in this work could rationalize the directionality observed in RNA-processing molecular machineries.

Related collections

Most cited references 19

Record: found
Abstract: found
Article: not found

Structural basis for DNA duplex separation by a superfamily-2 helicase.

Karl-Peter Hopfner, Sebastian Nehring, Julia K. Büttner (2007)

To reveal the mechanism of processive strand separation by superfamily-2 (SF2) 3'-->5' helicases, we determined apo and DNA-bound crystal structures of archaeal Hel308, a helicase that unwinds lagging strands and is related to human DNA polymerase theta. Our structure captures the duplex-unwinding reaction, shows that initial strand separation does not require ATP and identifies a prominent beta-hairpin loop as the unwinding element. Similar loops in hepatitis C virus NS3 helicase and RNA-decay factors support the idea that this duplex-unwinding mechanism is applicable to a broad subset of SF2 helicases. Comparison with ATP-bound SF2 enzymes suggests that ATP promotes processive unwinding of 1 base pair by ratchet-like transport of the 3' product strand. Our results provide a first structural framework for strand separation by processive SF2 3'-->5' helicases and reveal important mechanistic differences from SF1 helicases.

0 comments Cited 111 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Reconstructing the equilibrium Boltzmann distribution from well-tempered metadynamics.

M Bonomi, A Barducci, M Parrinello (2009)

Metadynamics is a widely used and successful method for reconstructing the free-energy surface of complex systems as a function of a small number of suitably chosen collective variables. This is achieved by biasing the dynamics of the system. The bias acting on the collective variables distorts the probability distribution of the other variables. Here we present a simple reweighting algorithm for recovering the unbiased probability distribution of any variable from a well-tempered metadynamics simulation. We show the efficiency of the reweighting procedure by reconstructing the distribution of the four backbone dihedral angles of alanine dipeptide from two and even one dimensional metadynamics simulation. 2009 Wiley Periodicals, Inc.

0 comments Cited 101 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Single-molecule experiments in vitro and in silico.

Marcos Sotomayor, Klaus Schulten (2007)

Single-molecule force experiments in vitro enable the characterization of the mechanical response of biological matter at the nanometer scale. However, they do not reveal the molecular mechanisms underlying mechanical function. These can only be readily studied through molecular dynamics simulations of atomic structural models: "in silico" (by computer analysis) single-molecule experiments. Steered molecular dynamics simulations, in which external forces are used to explore the response and function of macromolecules, have become a powerful tool complementing and guiding in vitro single-molecule experiments. The insights provided by in silico experiments are illustrated here through a review of recent research in three areas of protein mechanics: elasticity of the muscle protein titin and the extracellular matrix protein fibronectin; linker-mediated elasticity of the cytoskeleton protein spectrin; and elasticity of ankyrin repeats, a protein module found ubiquitously in cells but with an as-yet unclear function.

0 comments Cited 96 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Publication date Created: 27 March 2012

Article

DOI: 10.1021/ja210531q

ArXiV ID: 1203.5866

SO-VID: 363d84d5-2357-4bf2-b41f-b29dad3a3dd6

License:

http://arxiv.org/licenses/nonexclusive-distrib/1.0/

History

Custom metadata

Journal reference F. Colizzi and G. Bussi, J. Am. Chem. Soc. 132, 5173 (2012)

Comments Reprinted (adapted) with permission from J. Am. Chem. Soc., 2012, 134 (11), pp 5173-5179. Copyright (2012) American Chemical Society

RNA unwinding from reweighted pulling simulations

Read this article at

Abstract

Related collections

RNA drug delivery

Most cited references 19

Structural basis for DNA duplex separation by a superfamily-2 helicase.

Reconstructing the equilibrium Boltzmann distribution from well-tempered metadynamics.

Single-molecule experiments in vitro and in silico.

Author and article information

Journal

Article

History

Custom metadata

Comments

Comment on this article

Similar content 113

Cited by 6

Most referenced authors 336