L3 LOOP-MEDIATED MECHANISMS OF PORE CLOSING IN PORIN - A MOLECULAR-DYNAMICS PERTURBATION APPROACH

L3 loop-mediated mechanisms for pore closing in porin are investigated with molecular dynamics simulation, using an approach that can be rel ated to the phenomenon of voltage gating, Voltage gating is seen as a perturbation of the electrostatic screening inside the porin pore wher e, by the influence of the potential gradient, water and counter-ion d istribution can be slightly displaced from their equilibrium distribut ion, This is simulated by perturbing the screening electrostatics of i onizable groups inside the pore, Under these conditions, a localized c onformational change takes place, involving 12 (Ile102- Ala113) out of the 44 residues of the loop, The pore is reduced to a sixth of ifs op en state size, The conformational change can be achieved with a small perturbation and it is reversible once the perturbation is switched of f (relaxation process), Other types of behaviour predominating at high er simulation temperatures are found for the loop, involving an extra conformational change in the Thr92-Asp96 loop segment. This conformati onal change completely closes the pore, but is not reversible under th e simulation conditions, Both zones involved in the conformational cha nges contain or overlap the zones which were described previously, usi ng other techniques, to be the most flexible zones of the loop.