title: EGFR Mutant Structural Database: computationally predicted 3D structures and the corresponding binding free energies with gefitinib and erlotinib.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation-induced drug resistance has caused great difficulties in the treatment of non-small-cell lung cancer (NSCLC). However, structural information is available for just a few EGFR mutants. In this study, we created an EGFR Mutant Structural Database (freely available at http://bcc.ee.cityu.edu.hk/data/EGFR.html ), including the 3D EGFR mutant structures and their corresponding binding free energies with two commonly used inhibitors (gefitinib and erlotinib).
  
  
  RESULTS
  We collected the information of 942 NSCLC patients belonging to 112 mutation types. These mutation types are divided into five groups (insertion, deletion, duplication, modification and substitution), and substitution accounts for 61.61% of the mutation types and 54.14% of all the patients. Among all the 942 patients, 388 cases experienced a mutation at residue site 858 with leucine replaced by arginine (L858R), making it the most common mutation type. Moreover, 36 (32.14%) mutation types occur at exon 19, and 419 (44.48%) patients carried a mutation at exon 21. In this study, we predicted the EGFR mutant structures using Rosetta with the collected mutation types. In addition, Amber was employed to refine the structures followed by calculating the binding free energies of mutant-drug complexes.
  
  
  CONCLUSIONS
  The EGFR Mutant Structural Database provides resources of 3D structures and the binding affinity with inhibitors, which can be used by other researchers to study NSCLC further and by medical doctors as reference for NSCLC treatment.
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong. lichunma2-c@my.cityu.edu.hk.
authors.forename: Lichun
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong. danwang6-c@my.cityu.edu.hk.
authors.forename: Debby D
authors.initials: DD
authors.lastname: Wang
authors.affiliation: School of Computer Science and Technology, Soochow University, Suzhou, China. 149145459@qq.com.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Electronic Engineering, City University of Hong Kong, Kowloon, Hong Kong. h.yan@cityu.edu.hk.
authors.forename: Hong
authors.initials: H
authors.lastname: Yan
authors.affiliation: Li Ka Sing Faculty of Medicne, University of Hong Kong, Pokfulam, Hong Kong. mwpik@hku.hk.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Wong
authors.affiliation: Li Ka Sing Faculty of Medicne, University of Hong Kong, Pokfulam, Hong Kong. vhflee@hku.hk.
authors.forename: Victor H F
authors.initials: VH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D030562:Databases, Protein; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005091:Exons; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib