June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
IN SILICO COMPARISON OF RHO-KINASE INHIBITORS - PROTEIN DOCKING AFFINITY
Author Affiliations & Notes
  • Francisco Bandeira
    Federal University of Sao Paulo, Singapore, Singapore
    Tissue Engineering and Stem Cell, Singapore Eye Research Institute, Singapore, Singapore
  • Yossa Dwi Hartono
    Agency for Science, Technology and Research (A*STAR), Bioinformatics Institute, Singapore, Singapore
    National University of Singapore, Synthetic Biology for Clinical and Technological Innovation (SynCTI, Singapore, Singapore
  • Anandalakshmi Venkatraman
    Tissue Engineering and Stem Cell, Singapore Eye Research Institute, Singapore, Singapore
  • José Álvaro Pereira Gomes
    Federal University of Sao Paulo, Singapore, Singapore
  • Gary S L Peh
    Tissue Engineering and Stem Cell, Singapore Eye Research Institute, Singapore, Singapore
  • Jodhbir S Mehta
    Tissue Engineering and Stem Cell, Singapore Eye Research Institute, Singapore, Singapore
    Corneal and External Diseases Department, Singapore National Eye Centre, Singapore
  • Footnotes
    Commercial Relationships   Francisco Bandeira, None; Yossa Hartono, None; Anandalakshmi Venkatraman, None; José Álvaro Gomes, None; Gary Peh, None; Jodhbir Mehta, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1465. doi:
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    • Get Citation

      Francisco Bandeira, Yossa Dwi Hartono, Anandalakshmi Venkatraman, José Álvaro Pereira Gomes, Gary S L Peh, Jodhbir S Mehta; IN SILICO COMPARISON OF RHO-KINASE INHIBITORS - PROTEIN DOCKING AFFINITY. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1465.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Rho kinase inhibitors (ROCKi) possess pro-regenerative effects in corneal endothelial cells, as reported in ex vivoand in vivo models. There are several classes of commercially available ROCKi, however, only a few have been tested for corneal regenerative purposes. We have simulated protein docking of different ROCKi and compared their affinity for ROCK-1

Methods : Structures of ROCK-1 were obtained from the Protein Data Bank (PDB). Redundant structures were excluded (clustering cutoff of 0.51). Molecular docking was performed with Schrödinger 2018-2 Glide. The receptors were prepared with Protein Preparation Wizard and ligands with tautomeric and protonation states (LigPrep). For docking, extra precision (XP) mode was used.

Results : A set of 23 ROCK structures was found in the PDB, the maximum/minimum resolutions were of 3.4 Å/2.93 Å,. Seven ROCK-I non-redundant structure were selected for the binding assay .. Out of 46 compounds tested (20 isoquinolines, 15 aminofurazan, 6 benzodiazepine, 4 indazoles and 1 amide), 34 presented a significantly higher affinity for ROCK-1, when compared to Y-27632 (p<0.0001). All ROCKi classes presented a stronger mean docking score than Y-27632 (p<0.0001). The isoquinoline class represented 70% of the drugs within the top ten highest docking scores, with 3 compounds presenting a docking score stronger than -12. There were no significant differences among ROCKi other than Y27632.

Conclusions : There are several ROCKi from different classes with high affinity to ROCK. Their potential in endothelial regenerative treatments should be further investigated with in vitro and in vivo experiments.

This is a 2020 ARVO Annual Meeting abstract.

 

Mean Docking Affinity of different ROCKi for ROCK 1 and 2

Mean Docking Affinity of different ROCKi for ROCK 1 and 2

 

Bar chart comparing docking affinity of different ROCKi for ROCK 1 and 2

Bar chart comparing docking affinity of different ROCKi for ROCK 1 and 2

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