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10. Essential Dynamics of DNA Repair Enzyme T4 Endonuclease V
J.G. Siebers and Hiroshi Yamaguchi
Keywords: T4 endonuclease V, molecular dynamics, essential dynamics
The exposure of DNA to ultraviolet (UV) radiation is an important mechanism that causes the production of pyrimidine dimers which are lethal and mutagenic for organisms. T4 endonuclease V acts as a repair enzyme for the thymine photodimer lesions of double-stranded DNA. We have conducted a 600 ps molecular dynamics simulation, including 100 ps for temperature and density adjustment as well as system equilibration, to study the properties of this system in detail.
The essential dynamics (ED) method was used to reduce the multidimensional configurational space to a subspace of only about 10 degrees of freedom. To achieve this the C
backbone atoms were chosen to represent the slow motions of the protein. For this selection the average structure and the covariance matrix of the fluctuations about the average were calculated. Diagonalization of the covariance matrix gives eigenvectors and eigenvalues, where a small subset accounts for more than 90% of the overall vibrational motion of the protein. These eigenvectors span the essential subspace and are of particular interest.
The left hand drawing in Fig. 8 shows the secondary structure of T4 endonuclease V obtained from crystallographic data along with its water accessible surface. For the active sites GLU23, ARG3, ARG22, and ARG26, the side chain atoms are also displayed. The right hand drawing shows snapshots of the C atoms moving along the first essential eigenvector. We note the relative rigidity of the protein in the region of the active sites.
In the next step of this study we will compare the essential subspaces of T4 endonuclease V with the essential subspaces of the mutants E23Q and R3Q.
atoms moving along the first essential eigenvector.