Chemotaxis PathwayHow can physics help?

Davi Ortega

Summary• Vocabulary

– Pathway, Proteins, Peptides, Amino acids.– Genome, Sequences, Multiple Alignment.

• Bacteria (E. Coli)– Chemotaxis pathway.– Motility, Substances gradient recognition.

• The proteins interaction problem– CheA, CheW and MCP

• Methods and Evidences– Multiple Alignment– Docking – Molecular Dynamics.

• Conclusions

Vocabulary

• Amino Acids– In chemistry, an amino acid is a molecule that contains both amine and

carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula NH2CHRCOOH.

In Biology•20 Amino Acids

• Identified by three Letter code or one Letter Code

•Classified by biochemistry properties: Polar, Hydrophobic and Charged

Vocabulary

• Peptides– Chain of Amino Acids connected by the peptide bonds

…FSEK…

Vocabulary• Proteins

– Chain of Amino Acids that when folded execute a biological function.

Vocabulary• Pathway

– Set of protein that works cooperatively with the same objective

Vocabulary• Genome: the whole hereditary information encoded on the DNA• Sequence: Sequence of the amino acids decoded from the DNA.• Multiple Alignment: Alignment of different sequences of the same

protein.

Constant probability of mutations at any Residue.

Conserved residues must be extremely important to the biological function

E. Coli• Chemotaxis pathway

– Senses the external environment and actuates on the motility system

Bacteria Flagella Motility

Movie

The interaction problem• The structures of CheA, CheW and MCP

The interaction problem• The same organism has several CheA, CheW and MCP.

– How do they interact!?– How do they cluster?– What kind of signal is transmitted?– Which CheA interacts with which CheW and MCPs ?

Methods: Multiple Alignment

CheA

CheWMCP

3D Structures & Molecular Dynamics

• Molecular Dynamics– Force Field techniques.

• 3D Structures are snapshots– Few structures available– Need to have energy minimized– Simulation with non zero temperature.

Docking (by biochemistry and sequences)

• Based on affinity of amino acids.– 1) Define the contacts aminoacids– 2) Produce a score based on the affinity for each sequence.– 3) Score the possible matches

– 4) Select the best scores.

Conclusion

• Chemotaxis Pathway: Interactions between proteins are still a open problem

• Physics, Biology (and Genomics), Chemistry and Computation can solve the mystery.

• Solutions can leads to better antibiotics or bioengineering bacteria to increase biofuel efficiency.