QTY Reform

1 Introduction

QTY-code¹ enables transmembrane proteins to become water-soluble without the need for detergents by replacing hydrophobic residues in α-helices with hydrophilic ones, while still preserving their structure and function. This provides a new tool for studying these important receptors and holds promise for applications in drug design and therapeutic development. Additionally, QTY-code has been functionally validated on antibodies. Researchers applied QTY design to β-sheet structures in four antibodies and found that the variants exhibited significantly reduced aggregation propensity. Molecular dynamics simulations also showed preserved antigen-binding affinity and structural stability². This suggests that QTY-code has strong potential in mitigating antibody aggregation and offers a new approach for optimizing the stability of antibody-based drugs.

QTY Reform is a protein structure modification tool based on the QTY-code principle, designed to replace hydrophobic amino acids in specific secondary structure regions (α-helix or β-sheet) of target proteins with hydrophilic amino acids.

Implementation details are as follows:

• Secondary Structure Identification
  Using the DSSP algorithm to identify α-helices and β-sheets by parsing the PDB file, enabling precise segmentation of secondary structures.

• Execution of QTY-code (Amino Acid Substitution)
  LEU -> GLN (Leucine replaced by Glutamine).
  ILE -> THR (Isoleucine replaced by Threonine).
  VAL -> THR (Valine replaced by Threonine).
  PHE -> TYR (Phenylalanine replaced by Tyrosine).

• Structure Prediction and Reconstruction
  Generate the three-dimensional structure of the modified antibody using the deep learning algorithm ImmuneBuilder³ and the IMGT numbering scheme.

Parameter

• ProteinType: Specify the type of target protein (Antibody or Nanobody).
• PDBfile: Input PDB file.
• HeavyChainID/LightChainID: Specify the heavy and light chain IDs of the antibody (nanobodies require only the heavy chain).
• RegionToReplace: Select the secondary structure region to be modified (α-helix or β-sheet).

Result Explanation

• FASTA file: Contains the modified amino acid sequence.
• PDB file: AI-predicted three-dimensional structure of the modified antibody.
• Chain Naming Rule: Antibodies retain the default H/L chain identifiers, while nanobodies are uniformly labeled as H chains.

Reference