1. Modeling Biomolecules Using the WWW

2. Major Classes of Biomolecules n Peptides (Proteins) n Carbohydrates n Nucleic Acids n Lipids

3. Modeling Peptides n Primary structure – Most molecular modeling software allows construction of peptide models by appending pre-constructed amino acids in sequence, usually by selecting their 1- or 3- letter abbreviations. n Secondary structure – features such as  -helix,  (pleated) sheet, hairpin turns, etc. can be specified (examples on following panel).

4. Alpha Helix Secondary Structure

5. Beta Sheet Secondary Structure

6. Hairpin Turn Secondary Structure Hairpin turn, Beta sheet Hairpin turn, alpha helix

7. Modeling Peptides... n Tertiary structure – folding of chains…more difficult to model accurately, unless structure is known from X-ray or NMR. n Quaternary structure – Combination of several subunits...likewise difficult to model accurately, unless structure is known from X-ray or NMR.

8. Modeling Peptides... n Computations are usually limited to molecular mechanics, although semi- empirical MO calculations can be performed on small biopolymers. n MM Forcefields designed for biomolecules: – Amber (peptides and nucleic acids)/Kollman – OPLS (peptides and nucleic acids)/Jorgensen – BIO+ (biomacromolecules)/Karplus (all of these are found in HyperChem)

9. Modeling Biomolecules using HyperChem

10. HyperChem n Special database for Peptides n 20 Pre-optimized amino acids n Peptide menu choices –  helix –  (pleated) sheet – other n Termination modes: – NH 2 or NH 3 + ; CO 2 H or CO 2 -

11. Spartan n Special database for Nucleotides n 4 Pre-optimized bases (A,T,C,G) n Nucleotide menu choices – DNA (double strand), DNA (single strand) – RNA (double strand), RNA (single strand) – DNA-RNA mixed n A, B or Z helical forms (differ in rise/base)

12. WWW pages dealing with Modeling Biomolecules n Georgia State University molecular modeling site: modeling problems, biomolecules: http://heme.gsu.edu/glactone/ http://heme.gsu.edu/glactone/ n Dr. Barry Honig’s web site (Columbia University… great images of biomolecules): http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Main_Page http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Main_Page n

13. WWW pages dealing with Modeling Biomolecules... n Molecular Graphics (rendering); University of Geneva, Switzerland (Dr. Jacques Weber) http://scsg9.unige.ch/fln/eng/toc.html NIH Center for Molecular Modeling http://cmm.info.nih.gov/modeling/ http://cmm.info.nih.gov/modeling/

14. WWW pages dealing with Modeling Biomolecules... n Molecular Modeling Research Group at the Dept. of Agricultural Environmental Sciences and Food Biotechnology, University of Sassari - ITALY: http://antas.agraria.uniss.it http://antas.agraria.uniss.it n The Research Collaboratory for Structural Bioinformatics (PDB database of structures of proteins and other biomolecules): http://www.rcsb.org http://www.rcsb.org