By Mary Pulgar
This class was lectured by the professor Shuguang Zhang (MIT), who catched us with his amazing analogies to introduce us to the Protein Design world. I loved this one 'About 10,000 years ago, humans began to domesticate plants and animals. Now it's time to domesticate molecules.' - Susan Lindquist.
He started with a brief history of Protein design, then he talked about the importance of H-bonding and drove us to the concept of "water clathrate", as a way to encase molecules to become soluble. I also liked how he related the stone walls with protein structure. that is, the way they are built with different sizes, shapes, and properties of amino acids.
Prof. Zhang also discussed about the chiral forms in nature, remarking that L-form in the natural form. Finally he talked about coiled coil proteins.
Later on, Thras Karydis (DeepCure) presented us some topics in computational protein-design. He talked about solving protein folding, and related the protein nature with: the mechanism of evolution, co-evolution of protein, redundancy in functionality and efficient encoding in the genome. Thras showed us some sites regarding to proteins like: UniProtKB, PDB (Protein Data Bank), and NCBI. And talking about the Protein Universe, there are some levels of Protein Design, like Structure prediction, Fixed-backbone design, and De novo design. For this purpose, there are important tools like Molecular Dynamics Simulations, Monte-Carlo Sampling, and Learning-Based Structure Prediction.
PART A
Why are there only 20 natural amino acids?
Since DNA is read as a triplet or as a codon, each group encodes for 1 single amino acid. Then, there is likely to have 64 different combinations from the 4 bases (4^3=64). However, more than one codon codes for 1 amino acid. These codons are redundant, meaning that the degeneracy of the DNA allows ensuring accurate translation. Besides, this redundancy avoids point mutations.
On the other hand, 20 amino acids are enough for protein structure and function.
DEOXY HUMAN HEMOGLOBIN (HBB)
I chose the human hemoglobin (HBB) from Homo sapiens (human) because it turns out interesting for me due to the fact of having a central iron atom surrounded by 4 heme groups.
DOI: 10.2210/pdb1A3N/pdb Classification: OXYGEN TRANSPORT Organism(s): Homo sapiens Mutation(s): No Method: X-ray diffraction Resolution: 1.80 Å Released: 1998-04-29
Function: Involved in oxygen transport from the lung to the various peripheral tissues. LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.
The amino acid sequence of hemoglobin (subunit beta) was retrieved from UniprotKB and has a length of 147 amino acids:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPK
VKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFG
KEFTPPVQAAYQKVVAGVANALAHKYH
The most frequent amino acids are Leucine (L) and Valine (V), both with 18 repeats each. My protein belongs to the globin family. According to pBLAST it were found 250 homologous sequences.