Type
Text
Type
Dissertation
Advisor
Simmerling, Carlos | Rizzo, Robert | Tonge, Peter | Seeliger, Markus.
Date
2014-12-01
Keywords
Chemistry
Department
Department of Chemistry.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77138
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Generalized Born solvent model offers inexpensive approach for solvation energy calculation as compared to explicit solvent and Poisson-Boltzmann (PB) method. Thanks to its speed, GB models have been widely used in molecular dynamics (MD) simulations. However the speed comes with tradeoffs. Literatures have pointed out the weaknesses of GB models in inaccurately calculating solvation energy that leads to helical bias in protein simulation or unstable DNA/RNA duplex in nucleic acid simulation. Here we introduced the reparameterization of the recently developed GB-Neck model to improve its accuracy. Compared to other pairwise GB models (e.g. GB-OBC and GB-Neck) the new GB models have better agreement to very accurate (but slow) PB method in terms of reproducing solvation energies for a variety of systems from protein to nucleic acid. For the protein, secondary structure preferences are in much better agreement with explicit solvent simulations. We also obtain near-quantitative reproduction of experimental structure and thermal stability profiles for several model peptides. Moreover the model is able to reproduce the folding of microsecond to millisecond time scale folding of a series of larger proteins. For the nucleic acid, simulations maintain stable trajectories for various DNA and RNA duplexes through MD simulations and also correctly fold DNA/RNA hairpin from extended conformation. | 240 pages
Recommended Citation
Nguyen, Hai Minh, "Improved Generalized Born Solvent Model Parameters for Protein and Nucleic Acid Simulations" (2014). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2974.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2974