Home // BIOTECHNO 2023, The Fifteenth International Conference on Bioinformatics, Biocomputational Systems and Biotechnologies // View article

Analyzing Switch Regions of Human Rab7a and Rab10 by Molecular Dynamics Simulations

Authors:
Levy Bueno Alves
Sarah Sandy Sun
Silvana Giuliatti

Keywords: Small GTPases; structural flexibility; in silico

Abstract:
Rab7a and Rab10 are small GTPases that regulates cellular processes by alternating between its GDP-bound inactive and the GTP-bound active states. Studies have shown that functional deficiencies in the pathways of these enzymes are implicated in ciliophaties, cancer and neurodegenerative diseases. Thus, the modulation of the activity of these targets may represent an interesting strategy in drug discovery for the treatment of several human diseases. In order to identify potential Rab7a and Rab10 inhibitors, we studied the mobility of the switch1-interswitch-switch2 surface to understand the active “ON” and inactive “OFF” states of these enzymes. We use molecular dynamics simulations to investigate the atomic movements of the switch regions of these enzymes associated with GDP and GTP nucleotides. We found noticeable differences in the local flexibility of switch 1 when these Rab GTPases were bound to GDP. However, the deterministic method used was not able to successfully differentiate the flexibility of switch 2 region. We hypothesized that the flexibility of the switch 1 region can be used as an indicator of in silico studies that search potential competitive inhibitors based on nucleotides against these targets. Furthermore, the present study can be useful for research that involves the description on-to-off process of other target proteins.

Pages: 12 to 15

Copyright: Copyright (c) IARIA, 2023

Publication date: March 13, 2023

Published in: conference

ISSN: 2308-4383

ISBN: 978-1-68558-058-2

Location: Barcelona, Spain

Dates: from March 13, 2023 to March 17, 2023