Modeling Biomolecules Using the WWW

Major Classes of Biomolecules

Peptides (Proteins) Carbohydrates Nucleic Acids Lipids

Modeling Peptides

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.

Secondary structure– features such as -helix, (pleated) sheet, hairpin

turns, etc. can be specified (examples on following panel).

Alpha Helix Secondary Structure

Beta Sheet Secondary Structure

Hairpin Turn Secondary Structure

Hairpin turn, Beta sheet

Hairpin turn, alpha helix

Modeling Peptides...

Tertiary structure– folding of chains…more difficult to model

accurately, unless structure is known from X-ray or NMR.

Quaternary structure– Combination of several subunits...likewise

difficult to model accurately, unless structure is known from X-ray or NMR.

Modeling Peptides...

Computations are usually limited to molecular mechanics, although semi-empirical MO calculations can be performed on small biopolymers.

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)

Modeling Biomolecules using HyperChem

HyperChem

Special database for Peptides 20 Pre-optimized amino acids Peptide menu choices

– helix – (pleated) sheet– other

Termination modes: – NH2 or NH3

+; CO2H or CO2-

Spartan

Special database for Nucleotides 4 Pre-optimized bases (A,T,C,G) Nucleotide menu choices

– DNA (double strand), DNA (single strand)– RNA (double strand), RNA (single strand)– DNA-RNA mixed

A, B or Z helical forms (differ in rise/base)

WWW pages dealing with Modeling Biomolecules

Georgia State University molecular modeling site: modeling problems, biomolecules: http://heme.gsu.edu/glactone/

Dr. Barry Honig’s web site (Columbia University…

great images of biomolecules):http://wiki.c2b2.columbia.edu/honiglab_public/index.php/Main_Page

WWW pages dealing with Modeling Biomolecules...

Molecular Graphics (rendering); University of Geneva, Switzerland (Dr. Jacques Weber)

http://scsg9.unige.ch/fln/eng/toc.html

NIH Center for Molecular Modelinghttp://cmm.info.nih.gov/modeling/

WWW pages dealing with Modeling Biomolecules...

Molecular Modeling Research Group at the Dept. of Agricultural Environmental Sciences and Food Biotechnology, University of Sassari - ITALY:http://antas.agraria.uniss.it

The Research Collaboratory for Structural Bioinformatics (PDB database of structures of proteins and other biomolecules):http://www.rcsb.org