Refinando el análisis de estabilidad y cinético del desplegamiento de proteínas a partir de simulaciones de dinámica molecular

López Martínez, Daniel Eduardo
Galano Frutos, Juan José (dir.) ; Sancho Sanz, Javier (dir.)

Universidad de Zaragoza, CIEN, 2021

Máster Universitario en Biotecnología Cuantitativa

Abstract: In the present study, a method for detecting protein unfolding events and evaluating protein stability and kinetics from relaxation Molecular Dynamics (rMD) simulations has been fine tuned. In particular, a 2D root mean square deviation (RMSD)-based clustering was performed on trajectories generated by rMD simulations for the protein α3D under a broad range of temperatures and two different force fields: CHARMM27 and AMBER99SB-disp. The half-life of unfolding was measured from the clustering plots and its value was used to compute the conformational stability of the protein extrapolated at 298 K by means of an empirical model previously developed by the research group. Ladder- and ramp-based temperature scanning simulations were also explored to assess the optimum simulation approach in terms of computational resources, accuracy, and adequacy for the kind of protein stability and unfolding kinetics analyses here envisioned. Furthermore, the performance (accuracy and reliability) of the above-mentioned force fields was assessed in estimating protein stability.

Tipo de Trabajo Académico: Trabajo Fin de Master