engleski

Free Energy Landscape for Entrance Pathway of CoA into the Active Site of Pyruvate-Formate Lyase

Knowledge of how free energy of a certain process changes along the reaction coordinate has always been of great interest, both in chemistry and physics. Therefore, a lot of effort has been made in the direction of developing methods and computational tools to estimate potential of mean force. Several such methods implemented in the AMBER software package were used in the search of the possible entrance pathways of a ligand (CoA) into the active site of the protein (Pyruvate- Formate-Lyase). The conformational space of the system was explored by the umbrella sampling method and its variation, so called targeted MD. The latter method allows somewhat greater flexibility in the choice of the possible pathway by defining the reaction coordinate as structural RMS deviation between the final and initial conformation and could give rise to alternative pathways. As a complementary approach to these equilibrium methods, we have used steered dynamics to study the process by exposing it to non- equilibrium conditions, i.e. by doing the pulling experiments and using Crooks fluctuation theorem to extract the information about the free energy profile. Finally, the PMF obtained from all three approaches will be compared and discussed.

PFL; CoA; entrance channel; free energy; potential of mean force; molecular dynamics; umbrella sampling; steered molecular dynamics

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