Accelerated Construction of Kinetic Network Model of Biomolecules Using Steered Molecular Dynamics

Journal of Chemical Theory and Computation
Susmita GhoshSwati Bhattacharya

Abstract

A new class of rare event acceleration techniques based on steered molecular dynamics (SMD) simulations is introduced. A stretching force applied on a biomolecule causes it to access large end-to-end distances. Under these conditions the biomolecule undergoes rapid conformational changes that are rare at zero-force conditions. A theory describing kinetics of a biomolecule at various stretching forces is presented. Using the theory, a master-Markov state model (master-MSM) is constructed from rates frequently accessed over a small range of force conditions. The master-MSM is shown to be applicable over a wide range of force conditions. We demonstrate application of the theory to three different biomolecular systems, namely, deca-alanine, TBA (thrombin binding aptamer), and a RNA hairpin. The master-MSM is used to estimate the kinetics at zero-force conditions, i.e., on the unbiased free-energy landscape, resulting inasmuch as 2-6 orders-of-magnitude speed-up over standard molecular dynamics.

References

Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R F MacayaJ Feigon
Jul 2, 1999·Journal of Molecular Biology·G Colmenarejo, I Tinoco
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·E Paci, M Karplus
Jan 24, 2003·Nature·Carlos BustamanteSteven B Smith
Jul 21, 2004·Journal of Computational Chemistry·Alexander D Mackerell
Jul 23, 2004·The Journal of Chemical Physics·Sanghyun Park, Klaus Schulten
Jul 23, 2004·The Journal of Chemical Physics·Donald HamelbergJ Andrew McCammon
Oct 14, 2005·Journal of Computational Chemistry·James C PhillipsKlaus Schulten
Dec 3, 2005·The Journal of Chemical Physics·Marek Cieplak, Joanna I Sułkowska
Sep 7, 2006·Proteins·Anders Irbäck, Simon Mitternacht
Mar 3, 2007·Annual Review of Biophysics and Biomolecular Structure·William J GreenleafSteven M Block
Feb 1, 2008·The Journal of Physical Chemistry. B·Nicolae-Viorel Buchete, Gerhard Hummer
May 26, 2010·The Journal of Physical Chemistry. B·Jeffery B KlaudaRichard W Pastor
May 27, 2010·The Journal of Chemical Physics·Abhijit Chatterjee, Arthur F Voter
Sep 13, 2011·Methods in Molecular Biology·Thomas Bornschlögl, Matthias Rief
Mar 27, 2012·Annual Review of Biophysics·Iwijn De Vlaminck, Cees Dekker
Jun 16, 2012·The Journal of Chemical Physics·Gungor OzerRigoberto Hernandez
Oct 30, 2012·Journal of Chemical Information and Modeling·Weihua LiYun Tang
Mar 8, 2013·The Journal of Chemical Physics·Vijesh J Bhute, Abhijit Chatterjee
Jul 5, 2013·The Journal of Chemical Physics·Vijesh J Bhute, Abhijit Chatterjee
May 17, 2014·The Journal of Chemical Physics·Srikanth Divi, Abhijit Chatterjee
Jun 5, 2014·Annual Review of Biophysics·Michael T Woodside, Steven M Block
Dec 18, 2014·Biophysical Journal·Li SunJosé N Onuchic
Nov 13, 2012·Journal of Chemical Theory and Computation·Gungor OzerRigoberto Hernandez
Jul 28, 2016·The Journal of Chemical Physics·Venkataramana Imandi, Abhijit Chatterjee
Feb 23, 2017·Journal of Chemical Theory and Computation·Susmita GhoshSwati Bhattacharya
Oct 23, 2017·The Journal of Chemical Physics·Arti BhoutekarAbhijit Chatterjee

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Citations

Feb 3, 2019·The Journal of Chemical Physics·Swati Bhattacharya, Abhijit Chatterjee

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