Publication detail

Toward structure-based drug design against the epidermal growth factor receptor (EGFR)

HADDAD, Y. REMEŠ, M. ADAM, V. HEGER, Z.

Original Title

Toward structure-based drug design against the epidermal growth factor receptor (EGFR)

Type

journal article in Web of Science

Language

English

Original Abstract

Most of the available crystal structures of epidermal growth factor receptor (EGFR) kinase domain, bound to drug inhibitors, originated from ligand-based drug design studies. Here, we used variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. The families shared similar mutational profiles and similarity in the ligand R-groups (chemical composition, geometry, and charge) facing the C-helix, mutation sites, and DFG domain. For structure-based drug design, we recommend a systematic decision-making process for choice of template, guided by appropriate pairwise fitting and clustering before the molecular docking step. Alternatively, the binding site shape/volume can be used to filter and select the compound libraries.

Keywords

Structure-Based Drug Design; epidermal growth factor receptor (EGFR); kinase domain; molecular docking

Authors

HADDAD, Y.; REMEŠ, M.; ADAM, V.; HEGER, Z.

Released

28. 2. 2021

ISBN

1359-6446

Periodical

DRUG DISCOVERY TODAY

Year of study

26

Number

2

State

United Kingdom of Great Britain and Northern Ireland

Pages from

289

Pages to

295

Pages count

7

URL

https://www.sciencedirect.com/science/article/pii/S1359644620304220

BibTex

@article{BUT170589,
  author="Yazan Abdulmajeed Eyadh {Haddad} and Marek {Remeš} and Vojtěch {Adam} and Zbyněk {Heger}",
  title="Toward structure-based drug design against the epidermal growth factor receptor (EGFR)",
  journal="DRUG DISCOVERY TODAY",
  year="2021",
  volume="26",
  number="2",
  pages="289--295",
  doi="10.1016/j.drudis.2020.10.007",
  issn="1359-6446",
  url="https://www.sciencedirect.com/science/article/pii/S1359644620304220"
}