Dinámica molecular de grano grueso de la proteína tau


  • Luciano Robert-Jimenez Instituto Tecnólogico Superior de Xalapa
  • Susana Figueroa-Gerstenmaier Universidad de Guanajuato
  • Gustavo Basurto-Islas Universidad de Guanajuato
  • Salvador Herrera-Velarde Instituto Tecnologico Superior de Xalapa




Alzheimer disease, intrinsic disorder protein, coarse-grained modelling, SIRAH.


Currently about 48 million people worldwide live with Alzheimer's disease, the most common form of dementia, and still without cure. This disease is partially due to abnormal posttranslational modifications in the protein tau, that in turn induce its abnormal polymerization, forming fibrils and neurofibrillary tangles. Tau does not have a well-defined structure, known as intrinsically disordered protein. Molecular dynamics is an effective method to study this kind of protein. In this work, molecular dynamics with SIRAH (Southamerican Initiative for a Rapid and Accurate Hamiltonian) force field was employed to model two different systems of tau, each with two protein molecules. In the first system, the two proteins are immersed only in water (represented as an explicit solvent), in the second system, in addition to the solvent, ions were added to investigate if charges presence induce protein self-aggregation. The structural modifications of tau were evaluated from 1 µs trajectory at 310 K. For each system, the proteins showed important changes with respect to the initial configuration; there are some differences in the secondary structure according to the presence or absence of ions. We identify that, in both systems, there is no evidence of tau aggregation. The results validated the use of the SIRAH force field to study large proteins and the capacity to reach temporal and spatial scales close to the experimental studies. In addition, the conformational analysis of the obtained trajectories suggests, for the first time, a molecular dynamics perspective that contributes to the understanding and identification of protein-protein interaction regions.

Actualmente, a nivel mundial, alrededor de 48 millones de personas padecen la enfermedad de Alzheimer, la forma más común de demencia, para la cual no hay cura. La enfermedad se debe, parcialmente, a las alteraciones postraduccionales que experimenta la proteína tau y que favorecen su polimerización anormal formando fibrillas y marañas neurofibrilares. La tau es una proteína intrínsecamente desordenada, es decir, no posee una estructura bien definida. Una técnica eficaz en el estudio de este tipo de proteínas es la dinámica molecular. En este trabajo se utilizó dinámica molecular empleando el campo de fuerza SIRAH (del inglés: Southamerican Initiative for a Rapid and Accurate Hamiltonian) para modelar dos sistemas distintos de tau, cada uno con dos moléculas de proteína. En el primer sistema las dos proteínas están inmersas únicamente en agua (representada como solvente explícito) y en el segundo sistema, además del solvente, se agregaron iones para investigar la influencia de cargas en la posible agregación de tau. A partir de la trayectoria de 1 μs a una temperatura de 310 K, se analizaron los cambios estructurales que experimentaron los monómeros de tau. En ambos sistemas, las proteínas presentaron cambios importantes respecto a la configuración inicial; existiendo algunas diferencias en la estructura secundaria acorde a la presencia o ausencia de iones. Identificamos que, en ambos sistemas, no hay evidencia de un proceso agregativo. Los resultados validaron el uso del campo de fuerza SIRAH para estudiar proteínas de gran tamaño y la factibilidad de alcanzar escalas temporales y espaciales cercanas a las experimentales. Además, el análisis conformacional de las trayectorias obtenidas ofrece, por primera vez, una perspectiva desde la dinámica molecular de la forma en que interactúan dos proteínas tau completas, lo cual contribuye a la comprensión del fenómeno y a la identificación de las regiones de interacción proteína-proteína.


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How to Cite

L. Robert-Jimenez, S. Figueroa-Gerstenmaier, G. Basurto-Islas, and S. Herrera-Velarde, “Dinámica molecular de grano grueso de la proteína tau”, Rev. Mex. Fís., vol. 69, no. 3 May-Jun, pp. 031701 1–, May 2023.



17 Thermodynamics and Statistical Physics