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Fall 2007
| Title: Pivots and flexibility in proteins |
| Speaker: Lilianne Dupuis |
| Affiliation: Departement de physique, Universite de Montreal |
| Date: December 4, 2007, 12:30 PM Eastern Time |
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| Abstract: Flexibility is a property inherent to the function of a protein. To understand the way it accomplishes its work, we need to see how the protein conformation changes when it enter in contact with a ligand for enzymatic purposes or with other proteins during formation of complexes. In the protein organization, we can distinguish highly regular regions, or secondary structures, linked together by irregular loops. Secondary structures are like blocks sticking together to form the tertiary structure. The approach we are developing uses a two-level description based on secondary structures. We compute their movement at a higher level of approximation, moving them as elastic blocks. Complex movements are then reserved to the irregular parts. This allows us to avoid local changes when we travel in the conformation space during the simulations. Our higher level is based on secondary structures because they can easily be reevaluated on the fly between each event, allowing us to perform dynamical coarse graining. Their regularity also permits elastic movement (expansion, contraction, torsion) along with rigid movements (translation, swiveling, rotation). We use a real force field to perform these moves, computing consensus block forces from atomic forces. Tests on a single set of pivots have established that the optimal pivot is not always near the border between the all-atom and an elastic block or secondary structure. We get better results by performing a dynamic optimization of the pivot placement all along the simulation. This can be done by establishing a distinction between coarse graining and ensemble move. In protein, a long-range move always implies a sensible change of the torsion angles phi and psi bordering one or several CA of the protein main chain. This mean that for each of them, the entire protein part that is preceding it will swivel relatively to the entire protein part following it. Secondary structures may be kept intact during the simulation of a long-range movement, but any CA of the flexible loops,or several of them, may be the pivots of this movement. We therefore reformulate the ART convergence method a holographic view of the molecule forces for each of the free CA pivots viewpoint, enhancing the detection of the psi and phi angles modifications that serve the best interest of the whole molecule. |
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