Unraveling the mechanisms of ribozyme catalysis with multiscale simulations

Tai Sung Lee, George M. Giambaşu, Adam Moser, Kwangho Nam, Carlos Silva-Lopez, Francesca Guerra, Olalla Nieto-Faza, Timothy J. Giese, Jiali Gao, Darrin M. York

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Description of a multiscale simulation strategy we have developed to attack problems of RNA catalysis is presented. Ribozyme systems give special challenges not present in typical protein systems, and consequently demand new methods. The main methodological components are herein summarized, including the assembly of the QCRNA database, parameterization of the AM1/d-PhoT Hamiltonian, and development of new semiempirical functional forms for improved charge-dependent response properties, methods for coupling many-body exchange, correlation and dispersion into the QM/MM interaction, and generalized methods for linear-scaling electrostatics, solvation and solvent boundary potentials. Results for a series of case studies ranging from noncatalytic reaction models that compare the effect of new DFT functionals, and on catalytic RNA systems including the hairpin, hammerhead and L1 ligase ribozymes are discussed.

Original languageEnglish (US)
Title of host publicationChallenges and Advances in Computational Chemistry and Physics
PublisherSpringer
Pages377-408
Number of pages32
DOIs
StatePublished - Jan 1 2009

Publication series

NameChallenges and Advances in Computational Chemistry and Physics
Volume7

Fingerprint

Catalytic RNA
parameterization
functionals
Catalysis
attack
catalysis
solvation
assembly
electrostatics
proteins
scaling
Hamiltonians
simulation
Solvation
interactions
Ligases
Parameterization
RNA
Discrete Fourier transforms
Electrostatics

All Science Journal Classification (ASJC) codes

  • Chemistry (miscellaneous)
  • Computer Science Applications
  • Physics and Astronomy (miscellaneous)

Keywords

  • DFT functional
  • linear-scaling method
  • multiscale simulation
  • QM/MM
  • Ribozyme catalysis

Cite this

Lee, T. S., Giambaşu, G. M., Moser, A., Nam, K., Silva-Lopez, C., Guerra, F., ... York, D. M. (2009). Unraveling the mechanisms of ribozyme catalysis with multiscale simulations. In Challenges and Advances in Computational Chemistry and Physics (pp. 377-408). (Challenges and Advances in Computational Chemistry and Physics; Vol. 7). Springer. https://doi.org/10.1007/978-1-4020-9956-4_14
Lee, Tai Sung ; Giambaşu, George M. ; Moser, Adam ; Nam, Kwangho ; Silva-Lopez, Carlos ; Guerra, Francesca ; Nieto-Faza, Olalla ; Giese, Timothy J. ; Gao, Jiali ; York, Darrin M. / Unraveling the mechanisms of ribozyme catalysis with multiscale simulations. Challenges and Advances in Computational Chemistry and Physics. Springer, 2009. pp. 377-408 (Challenges and Advances in Computational Chemistry and Physics).
@inbook{e0b44a7a2a7e4015b025353d33034e3c,
title = "Unraveling the mechanisms of ribozyme catalysis with multiscale simulations",
abstract = "Description of a multiscale simulation strategy we have developed to attack problems of RNA catalysis is presented. Ribozyme systems give special challenges not present in typical protein systems, and consequently demand new methods. The main methodological components are herein summarized, including the assembly of the QCRNA database, parameterization of the AM1/d-PhoT Hamiltonian, and development of new semiempirical functional forms for improved charge-dependent response properties, methods for coupling many-body exchange, correlation and dispersion into the QM/MM interaction, and generalized methods for linear-scaling electrostatics, solvation and solvent boundary potentials. Results for a series of case studies ranging from noncatalytic reaction models that compare the effect of new DFT functionals, and on catalytic RNA systems including the hairpin, hammerhead and L1 ligase ribozymes are discussed.",
keywords = "DFT functional, linear-scaling method, multiscale simulation, QM/MM, Ribozyme catalysis",
author = "Lee, {Tai Sung} and Giambaşu, {George M.} and Adam Moser and Kwangho Nam and Carlos Silva-Lopez and Francesca Guerra and Olalla Nieto-Faza and Giese, {Timothy J.} and Jiali Gao and York, {Darrin M.}",
year = "2009",
month = "1",
day = "1",
doi = "https://doi.org/10.1007/978-1-4020-9956-4_14",
language = "English (US)",
series = "Challenges and Advances in Computational Chemistry and Physics",
publisher = "Springer",
pages = "377--408",
booktitle = "Challenges and Advances in Computational Chemistry and Physics",

}

Lee, TS, Giambaşu, GM, Moser, A, Nam, K, Silva-Lopez, C, Guerra, F, Nieto-Faza, O, Giese, TJ, Gao, J & York, DM 2009, Unraveling the mechanisms of ribozyme catalysis with multiscale simulations. in Challenges and Advances in Computational Chemistry and Physics. Challenges and Advances in Computational Chemistry and Physics, vol. 7, Springer, pp. 377-408. https://doi.org/10.1007/978-1-4020-9956-4_14

Unraveling the mechanisms of ribozyme catalysis with multiscale simulations. / Lee, Tai Sung; Giambaşu, George M.; Moser, Adam; Nam, Kwangho; Silva-Lopez, Carlos; Guerra, Francesca; Nieto-Faza, Olalla; Giese, Timothy J.; Gao, Jiali; York, Darrin M.

Challenges and Advances in Computational Chemistry and Physics. Springer, 2009. p. 377-408 (Challenges and Advances in Computational Chemistry and Physics; Vol. 7).

Research output: Chapter in Book/Report/Conference proceedingChapter

TY - CHAP

T1 - Unraveling the mechanisms of ribozyme catalysis with multiscale simulations

AU - Lee, Tai Sung

AU - Giambaşu, George M.

AU - Moser, Adam

AU - Nam, Kwangho

AU - Silva-Lopez, Carlos

AU - Guerra, Francesca

AU - Nieto-Faza, Olalla

AU - Giese, Timothy J.

AU - Gao, Jiali

AU - York, Darrin M.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Description of a multiscale simulation strategy we have developed to attack problems of RNA catalysis is presented. Ribozyme systems give special challenges not present in typical protein systems, and consequently demand new methods. The main methodological components are herein summarized, including the assembly of the QCRNA database, parameterization of the AM1/d-PhoT Hamiltonian, and development of new semiempirical functional forms for improved charge-dependent response properties, methods for coupling many-body exchange, correlation and dispersion into the QM/MM interaction, and generalized methods for linear-scaling electrostatics, solvation and solvent boundary potentials. Results for a series of case studies ranging from noncatalytic reaction models that compare the effect of new DFT functionals, and on catalytic RNA systems including the hairpin, hammerhead and L1 ligase ribozymes are discussed.

AB - Description of a multiscale simulation strategy we have developed to attack problems of RNA catalysis is presented. Ribozyme systems give special challenges not present in typical protein systems, and consequently demand new methods. The main methodological components are herein summarized, including the assembly of the QCRNA database, parameterization of the AM1/d-PhoT Hamiltonian, and development of new semiempirical functional forms for improved charge-dependent response properties, methods for coupling many-body exchange, correlation and dispersion into the QM/MM interaction, and generalized methods for linear-scaling electrostatics, solvation and solvent boundary potentials. Results for a series of case studies ranging from noncatalytic reaction models that compare the effect of new DFT functionals, and on catalytic RNA systems including the hairpin, hammerhead and L1 ligase ribozymes are discussed.

KW - DFT functional

KW - linear-scaling method

KW - multiscale simulation

KW - QM/MM

KW - Ribozyme catalysis

UR - http://www.scopus.com/inward/record.url?scp=85073160518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073160518&partnerID=8YFLogxK

U2 - https://doi.org/10.1007/978-1-4020-9956-4_14

DO - https://doi.org/10.1007/978-1-4020-9956-4_14

M3 - Chapter

T3 - Challenges and Advances in Computational Chemistry and Physics

SP - 377

EP - 408

BT - Challenges and Advances in Computational Chemistry and Physics

PB - Springer

ER -

Lee TS, Giambaşu GM, Moser A, Nam K, Silva-Lopez C, Guerra F et al. Unraveling the mechanisms of ribozyme catalysis with multiscale simulations. In Challenges and Advances in Computational Chemistry and Physics. Springer. 2009. p. 377-408. (Challenges and Advances in Computational Chemistry and Physics). https://doi.org/10.1007/978-1-4020-9956-4_14