Journal
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
Volume 9, Issue 9, Pages 4243-4256Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ct400387r
Keywords
-
Funding
- FCT Ciencia
- POPH, QREN
- MES
- European Social Fund
Ask authors/readers for more resources
Proteins and protein-based complexes are the basis of many key systems in nature and have been the subject of intense research in the last decades, in an attempt to acquire comprehensive knowledge of reactions that take place in nature. Computational Alanine Scanning Mutagenesis approaches have been extensively used in the study of protein interfaces and in the determination of the most important residues for complex formation, the Hot-spots. However, as it is usually applied to the study of protein-protein interfaces, we tried to modify and apply it to the study of protein-DNA interfaces, which are also crucial in nature but have not been the subject of as much research. In this work, we carry out MD simulations of seven protein-DNA complexes and tested the influence of the variation of different parameters on the determination of the binding free energy terms (Delta Delta G(binding)) of 78 mutations: solvent representation, internal dielectric constant, Linear and Nonlinear Poisson-Boltzmann equation, Generalized Born model, simulation time, number of structures analyzed, number of MD trajectories, force field used, and energetic terms involved. Overall, this new approach gave an average error of 1.55 kcal/mol, and P, R, F1, accuracy, and specificity values of 0.78, 0.50, 0.61, 0.77, and 0.92, respectively. This improved computational alanine scanning mutagenesis approach may serve as a tool to explore the behavior of this important class of complexes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available