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Native state dynamics and mechanical properties of human topoisomerase I within a structure‐based coarse‐grained model
Author(s) -
Szklarczyk Oliwia,
Staroń Krzysztof,
Cieplak Marek
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22450
Subject(s) - molecular dynamics , native state , protein structure , topoisomerase , chemistry , biophysics , atom (system on chip) , protein dynamics , hinge , chemical physics , crystallography , stereochemistry , enzyme , computational chemistry , physics , biology , biochemistry , computer science , classical mechanics , embedded system
A coarse grained molecular dynamics model with an implicit solvent is used to elucidate properties of the human topoisomerase I. The model is defined through the native structure and it allows covering significantly longer time scales than in all atom simulations. Single residue and double residue motional characteristics are studied. The results are consistent with all atom simulations reported in the literature indicating usefulness of the model in further studies of this protein. Novel findings include broadening of the description of the dynamic behavior of the lip and hinge regions and a characterization of the motional properties of the RRM binding site of the enzyme. We also consider mechanical stretching of the protein and identify sources of the force peaks. The elastic properties of topoisomerase I are predicted to be average in comparison to other proteins, yielding a maximum force of resistance to pulling which should be of order 120 pN. The contact unraveling pattern is consistent with the understanding of the structure and function of the protein. We find supporting evidence for the hypothesis that the C‐terminal domain acquires an ordered structure upon binding with the core enzyme even though it forms a molten globule when in isolation. Proteins 2009. © 2009 Wiley‐Liss, Inc.