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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Beierlein F, Kneale GG, Clark T
Zeitschrift: Biophysical Journal
Verlag: Elsevier (Cell Press) / Biophysical Society
Jahr der Veröffentlichung: 2011
Band: 101
Seitenbereich: 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-Autoren / FAU-Herausgeber

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


Zusätzliche Organisationseinheit(en)
Exzellenz-Cluster Engineering of Advanced Materials


Autor(en) der externen Einrichtung(en)
University of Portsmouth


Zitierweisen

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: 

Zuletzt aktualisiert 2018-10-08 um 01:27