1. Homology modeling with SWISS-MODEL
Building of hER-beta in agonist conformation
Robert Dilis

2. Homology Modeling
Homology modeling allows to build the structure of a protein when only its amino acid sequence and the complete atomic structure of at least one other reference protein is known
The reference protein must be structurally homologous to the model protein being build. Structural segments, which are thought to be conserved within the family of homologous proteins are taken directly from the reference protein

3. Homology Modeling with SWISS-MODEL
SWISS-MODEL is a fully automated protein structure homology modeling server
Accessible via the ExPASy Molecular Biology web server (
Also accessible from DeepView (Swiss Pdb-Viewer) program
DeepView provides manual control during homology modeling and tools for analyzing generated models

4. Swiss-model provides two ways of doing homology modeling
First approach mode fully automatic procedure
Optimize Mode manually optimized sequence alignment via DeepView program(Swiss Pdb-Viewer)

5. Performing Homology modeling with SWISS-MODEL
Search for suitable templates
Check sequence identity with target
Create ProModII jobs
Generate models with ProModII This step involves several procedures performed by server:

6. Performing Homology modeling with SWISS-MODEL
Superposition of related 3D-structures
Generation of a multiple alignment with the sequence to be modeled
Generation of a framework for the new sequence
Rebuilding lacking loops
Completion and correction of backbone
Verification of model structure quality and packing
Energy minimization with Cromos96

7. Oestrogen receptor
The sex steroid hormone oestrogen exerts a wide variety of tissue-specific effects during growth and development
These effects are mediated by the oestrogen receptor (ER) – a ligand-inducible transcription factor belonging to the nuclear receptor (NR) superfamily
Such receptors share a common structural organization with distinct domains associated with DNA binding and hormone recognition
Hormone binding initiates a series of conformational changes within the receptor and enables ER to interact efficiently with its specific DNA response element and to recruit components of the transcriptional machinery

8. Oestrogen receptor Two isoforms of ER are known: ER- α and ER-
They exhibit overlapping but distinct tissue distribution patterns and differ in their ligand binding affinity and transactivational properties
ER-α and ER- share modest overall sequence identity (47%)
little homology between N-terminal transactivation (AF-1) domains
well conserved DNA- and ligand-binding domains
The C-terminal ligand-binding domain is multifunctional and in addition to a ligand binding cavity, contains region for receptor dimerization and ligand depended (AF-2) transactivation

9. Homology modeling of hER- LBD in agonist conformation using hER-α LBD template
First step is obtaining sequence in FASTA format of hER  LBD (1L2J:A) Can be obtained in Protein Data Bank (
Next step is obtaining template structure in agonist conformation (1G50:A) Can be obtained with Search template option in SWISS-MODEL (