Predicting the Effects of Basepair Mutations in DNA-Protein Complexes by Thermodynamic Integration

Journal article


Publication Details

Author(s): Beierlein F, Kneale GG, Clark T
Journal: Biophysical Journal
Publisher: Elsevier (Cell Press) / Biophysical Society
Publication year: 2011
Volume: 101
Pages range: 1130--1138
ISSN: 0006-3495


Abstract


Thermodynamically rigorous free energy methods in principle allow the exact computation of binding free energies in biological systems. Here, we use thermodynamic integration together with molecular dynamics simulations of a DNA-protein complex to compute relative binding free energies of a series of mutants of a protein-binding DNA operator sequence. A guanine-cytosine basepair that interacts strongly with the DNA-binding protein is mutated into adenine-thymine, cytosine-guanine, and thymine-adenine. It is shown that basepair mutations can be performed using a conservative protocol that gives error estimates of  10\% of the change in free energy of binding. Despite the high CPU-time requirements, this work opens the exciting opportunity of being able to perform basepair scans to investigate protein-DNA binding specificity in great detail computationally.



FAU Authors / FAU Editors

Beierlein, Frank Dr.
Computer-Chemie-Centrum
Clark, Timothy apl. Prof. Dr.
Computer-Chemie-Centrum


How to cite

APA:
Beierlein, F., Kneale, G.G., & Clark, T. (2011). Predicting the Effects of Basepair Mutations in DNA-Protein Complexes by Thermodynamic Integration. Biophysical Journal, 101, 1130--1138. https://dx.doi.org/10.1016/j.bpj.2011.07.003

MLA:
Beierlein, Frank, G. Geoff Kneale, and Timothy Clark. "Predicting the Effects of Basepair Mutations in DNA-Protein Complexes by Thermodynamic Integration." Biophysical Journal 101 (2011): 1130--1138.

BibTeX: 

Last updated on 2018-19-04 at 02:59