| Popis: |
All DNA Polymerases possess similar spatial features, functional properties, and have similar discrete state kinetic mechanisms to describe function. One of the fundamental goals in biophysics is to predict the mechanism, and eventually, the dynamics of protein function, from purely structural information. To this end, normal mode analysis is a well-established first step. In fact, the lowest frequency normal modes of proteins often correspond to the largest amplitude conformational changes, and are thus likely to play a dominant role in a protein's functional properties. We have both qualitatively and quantitatively explored the low frequency modes for the enzyme HIV1 Reverse Transcriptase, with and without DNA bound to the polymerase active site, using an Elastic Network model. We then compared the Elastic Network modes to those calculated from Essential Dynamics of nanosecond scale all-atom molecular dynamics simulations. From these comparisons we have isolated specific large amplitude modes of the protein corresponding to the fingers closing, in addition to other torsional oscillations, and assess equilibrium states for both free polymerases as well as those bound with dsDNA. |
