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 language||English (US)|
|Title of host publication||Challenges and Advances in Computational Chemistry and Physics|
|Number of pages||32|
|State||Published - 2009|
|Name||Challenges and Advances in Computational Chemistry and Physics|
Bibliographical notePublisher Copyright:
© Springer Science+Business Media B.V. 2009.
Copyright 2019 Elsevier B.V., All rights reserved.
- DFT functional
- Ribozyme catalysis
- linear-scaling method
- multiscale simulation