Proteomics & Genomics

Dr.
Asif
Proteomics & Genomics
Structural genomics &functional genomics
• Structural genomics is a field of genomics that involves the

characterization of genome structures.
• Study of physical nature of genomes that include sequence and
mapping of genes
• This knowledge can be useful in the practice of manipulating the
genes and DNA segments of a species.
• Structural genomics describes the 3-dimensional structure of each and
every protein that may be encoded by a genome – when specifically
analyzing proteins, this is more commonly referred to as structural
proteomics.
Structural genomics & Functional Genomics
• It involves high throughput DNA sequencing followed by assembly

organization and management of DNA sequences
• Structural genomics is an effort to determine the structures of all the
protein folds encoded by the genes in living organisms.
•
Goals
• One goal of structural genomics is to identify novel protein folds.

• Experimental methods of protein structure determination require
proteins that express and/or crystallize well, which may inherently
bias the kinds of proteins folds that this experimental data elucidate.
• A genomic, modeling-based approach such as ab initio modeling may
be better able to identify novel protein folds than the experimental
approaches because they are not limited by experimental constraints.
Methods
• Structural genomics takes advantage of completed genome sequences

in several ways in order to determine protein structures.
• The gene sequence of the target protein can also be compared to a
known sequence and structural information can then be inferred from
the known protein's structure.
• Structural genomics can be used to predict novel protein folds based
on other structural data.
• Structural genomics can also take modeling-based approach that relies
on homology between the unknown protein and a solved protein
structure.
de novo methods
• Completed genome sequences allow every open reading frame (ORF), the part of a
gene that is likely to contain the sequence for the messenger RNA and protein, to be
cloned and expressed as protein.
• These proteins are then purified and crystallized, and then subjected to one of two
types of structure determination: X-ray crystallography and nuclear magnetic
resonance (NMR).
• The whole genome sequence allows for the design of every primer required in order
to amplify all of the ORFs, clone them into bacteria, and then express them.
• By using a whole-genome approach to this traditional method of protein structure
determination, all of the proteins encoded by the genome can be expressed at once.
• This approach allows for the structural determination of every protein that is encoded
by the genome.
Modelling-based methods
• ab initio modeling
• This approach uses protein sequence data and the chemical and
physical interactions of the encoded amino acids to predict the 3-D
structures of proteins with no homology to solved protein structures.
One highly successful method for ab initio modeling is the Rosetta
program, which divides the protein into short segments and arranges
short polypeptide chain into a low-energy local conformation. Rosetta
is available for commercial use and for non-commercial use through
its public program, Robetta.
Sequence-based modeling
• This modeling technique compares the gene sequence of an unknown

protein with sequences of proteins with known structures. Depending on
the degree of similarity between the sequences, the structure of the known
protein can be used as a model for solving the structure of the unknown
protein. Highly accurate modeling is considered to require at least 50%
amino acid sequence identity between the unknown protein and the solved
structure. 30-50% sequence identity gives a model of intermediate-accuracy,
and sequence identity below 30% gives low-accuracy models. It has been
predicted that at least 16,000 protein structures will need to be determined
in order for all structural motifs to be represented at least once and thus
allowing the structure of any unknown protein to be solved accurately
through modeling
What is functional genomics?
• Functional genomics is the study of how genes and intergenic regions

of the genome contribute to different biological processes.
• A researcher in this field typically studies genes or regions on a
“genome-wide” scale (i.e. all or multiple genes/regions at the same
time), with the hope of narrowing them down to a list of candidate
genes or regions to analyze in more detail.
• Functional genomics is a field of molecular biology that attempts to
describe gene (and protein) functions and interactions
• The goal of functional genomics is to determine how the individual
components of a biological system work together to produce a
particular phenotype.
• Functional genomics focuses on the dynamic expression of gene
products in a specific context, for example, at a specific
developmental stage or during a disease.
• In functional genomics, we try to use our current knowledge of gene
function to develop a model linking genotype to phenotype.
There are several specific functional genomics approaches
depending on what we are focused on
• DNA level (genomics and epigenomics)

• RNA level (transcriptomics)
• Protein level (proteomics)
• Metabolite level (metabolomics)

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Dr.

• Structural genomics is a field of genomics that involves the

• It involves high throughput DNA sequencing followed by assembly

• One goal of structural genomics is to identify novel protein folds.

• Structural genomics takes advantage of completed genome sequences

• This modeling technique compares the gene sequence of an unknown

• Functional genomics is the study of how genes and intergenic regions

• DNA level (genomics and epigenomics)

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