Framework model for DNA polymerases.
DNA polymerases are complex machines with both chemical and mechanical functions. Recent crystal structures, ensemble kinetics, and single-molecule investigations have helped to elucidate the main properties of several DNA polymerases, all of which share common structural elements and a common basic mechanism, despite wide variations in amino acid sequence. The framework model is intended to aid in the understanding of these common features (and differences). It defines a class of models that automatically incorporates most of what is known about DNA polymerases within a single theoretical structure so that it is easier to make comparisons between them and to generate detailed models for specific polymerases. The framework model has three main elements: (1) a set of four key variables that describe the important motions within the protein-DNA-nucleotide complex, (2) a complete set of conformational states for the protein-DNA-nucleotide system, and (3) an approximate potential energy surface that controls the motions and transition rates between states. As an example application, we use the general framework ideas to build a detailed model for the HIV reverse transcriptase that is consistent with existing data, and predicts force-velocity curves and stepping-statistics histograms that can be directly compared to experiment.
Keller
David J
DJ
Molecular Machines Laboratory, Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131, USA. dkeller@unm.edu
Brozik
James A
JA
D000818:Animals; D003198:Computer Simulation; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D019384:Nucleic Acid Synthesis Inhibitors; D013329:Structure-Activity Relationship
D019384:Nucleic Acid Synthesis Inhibitors; D004259:DNA-Directed DNA Polymerase