Uploaded March 2025 | Updated September 2026, 43 minutes ago
Lecture by Professor Shuguang Zhang, MIT Media Lab, at the Molecular Frontiers Symposium "Frontiers of New Knowledge in Science" in Hong Kong, Nov 15-17, 2024.
ABSTRACT
Zhang Shuguang in 2011 conceived a simple QTY code to design water-soluble membrane proteins. There are ~26% genes that code for membrane proteins in human genome which are crucial for both internal and external cellular communications. The simple molecular QTY code is based on two key molecular structural facts: 1) all 20 amino acids are found in naturally occurring alpha-helices regardless of their distinct chemical properties: (i) hydrophilic, (ii) hydrophobic and (iii) amphiphilic; 2) several amino acids share striking structural similarities despite their different chemical properties; for example, Leucine (L) vs glutamine (Q); Valine (V) and Isoleucine (I) vs Threonine (T); and Phenylalanine (F) vs Tyrosine (Y). Using the simple QTY code, we replace ~50% hydrophobic amino acids L, I, V, F in transmembrane alpha-helices with hydrophilic amino acids Q, T, Y. The water-soluble QTY variants still maintain the stable structures and ligand-binding activities in the chemokine receptors, and 4 enzymatic functions of bacterial histidine kinase. The AphlaFold2 predictions proved the QTY code validity. The simple QTY code is a likely useful tool and has big impact on designs of watersoluble variants of previously water-insoluble GPCRs, glucose transporters, solute carrier transporters, ABC transporters, potassium ion channels, betabarrel outer membrane proteins and monoclonal antibodies. The AphlaFold2 and AlphaFold3 predictions proved the QTY code usefulness. The simple QTY code is a likely useful tool for designs of water-soluble variants for diverse applications.
Lecture by Professor Shuguang Zhang, MIT Media Lab, at the Molecular Frontiers Symposium "Frontiers of New Knowledge in Science" in Hong Kong, Nov 15-17, 2024.
ABSTRACT
Zhang Shuguang in 2011 conceived a simple QTY code to design water-soluble membrane proteins. There are ~26% genes that code for membrane proteins in human genome which are crucial for both internal and external cellular communications. The simple molecular QTY code is based on two key molecular structural facts: 1) all 20 amino acids are found in naturally occurring alpha-helices regardless of their distinct chemical properties: (i) hydrophilic, (ii) hydrophobic and (iii) amphiphilic; 2) several amino acids share striking structural similarities despite their different chemical properties; for example, Leucine (L) vs glutamine (Q); Valine (V) and Isoleucine (I) vs Threonine (T); and Phenylalanine (F) vs Tyrosine (Y). Using the simple QTY code, we replace ~50% hydrophobic amino acids L, I, V, F in transmembrane alpha-helices with hydrophilic amino acids Q, T, Y. The water-soluble QTY variants still maintain the stable structures and ligand-binding activities in the chemokine receptors, and 4 enzymatic functions of bacterial histidine kinase. The AphlaFold2 predictions proved the QTY code validity. The simple QTY code is a likely useful tool and has big impact on designs of watersoluble variants of previously water-insoluble GPCRs, glucose transporters, solute carrier transporters, ABC transporters, potassium ion channels, betabarrel outer membrane proteins and monoclonal antibodies. The AphlaFold2 and AlphaFold3 predictions proved the QTY code usefulness. The simple QTY code is a likely useful tool for designs of water-soluble variants for diverse applications.
