Molecular modeling of estrogen receptor using molecular operating environment

Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where undergraduates use modeling experiments to explore the structure of an estrogen receptor. We have employed the Molecular Operating Environment, a powerful molecular visualization software, which can be implemented on a variety of operating platforms. This tutorial reinforces the concepts of ligand binding, hydrophobicity, hydrogen bonding, and the properties of side chains and secondary structure taught in a general biochemistry class utilizing a protein that has importance in human biology.

[1]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[2]  Miss A.O. Penney (b) , 1974, The New Yale Book of Quotations.

[3]  K. Modarress,et al.  Evidence for involvement of tyrosine in estradiol binding by rat uterus estrogen receptor , 1991, The Journal of Steroid Biochemistry and Molecular Biology.

[4]  D C Richardson,et al.  The kinemage: A tool for scientific communication , 1992, Protein science : a publication of the Protein Society.

[5]  B. O’Malley,et al.  Molecular mechanisms of action of steroid/thyroid receptor superfamily members. , 1994, Annual review of biochemistry.

[6]  R A Sayle,et al.  RASMOL: biomolecular graphics for all. , 1995, Trends in biochemical sciences.

[7]  Donald Voet,et al.  Biochemistry, 2nd ed. , 1995 .

[8]  Zbigniew Dauter,et al.  Molecular basis of agonism and antagonism in the oestrogen receptor , 1997, Nature.

[9]  John A. Katzenellenbogen,et al.  The estradiol pharmacophore: Ligand structure-estrogen receptor binding affinity relationships and a model for the receptor binding site , 1997, Steroids.

[10]  D. A. Dougherty,et al.  The Cationminus signpi Interaction. , 1997, Chemical reviews.

[11]  P B Sigler,et al.  Crystallographic comparison of the estrogen and progesterone receptor's ligand binding domains. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  David A. Agard,et al.  The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen , 1998, Cell.

[13]  D. A. Dougherty,et al.  Cation-π interactions in structural biology , 1999 .

[14]  D. A. Dougherty,et al.  Cation-pi interactions in structural biology. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M Carlquist,et al.  Structure of the ligand‐binding domain of oestrogen receptor beta in the presence of a partial agonist and a full antagonist , 1999, The EMBO journal.

[16]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[17]  James R. Cox Teaching Noncovalent Interactions in the Biochemistry Curriculum through Molecular Visualization: The Search for pi Interactions , 2000 .

[18]  Steven W. Weiner,et al.  RasMol and Mage in the Undergraduate Biochemistry Curriculum , 2000 .

[19]  R. Hubbard,et al.  A structural biologist's view of the oestrogen receptor , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[20]  James R. Cox,et al.  Integrating Computational Chemistry into a Project-Oriented Biochemistry Laboratory Experience: A New Twist on the Lysozyme Experiment , 2001 .

[21]  Graham R. Parslow Commentary: Molecular visualization tools are good teaching aids when used appropriately , 2002 .

[22]  W. Delano The PyMOL Molecular Graphics System , 2002 .

[23]  J. Richardson,et al.  Teaching and assessing three-dimensional molecular literacy in undergraduate biochemistry , 2002 .

[24]  J. Richardson,et al.  Teaching molecular 3‐D literacy , 2002 .

[25]  Duane W. Sears Using inquiry‐based exercises and interactive visuals to teach protein structure/function relationships , 2002 .

[26]  Eric Martz,et al.  Protein Explorer: easy yet powerful macromolecular visualization. , 2002, Trends in biochemical sciences.

[27]  James R. Cox,et al.  Lesson plan for protein exploration in a large biochemistry class * , 2003 .

[28]  David Chandler,et al.  jAMVLE, A new integrated molecular visualization learning environment * , 2006, Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology.

[29]  Paul A Craig,et al.  EZ‐Viz, a tool for simplifying molecular viewing in PyMOL , 2006, Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology.

[30]  Angel Herráez,et al.  Biomolecules in the computer: Jmol to the rescue , 2006, Biochemistry and molecular biology education : a bimonthly publication of the International Union of Biochemistry and Molecular Biology.