Cyclic Peptide Initial Conformation Using Circular Cα Arrangement
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Solution Overview
Problem
The challenge in searching for a stable conformation of a cyclic peptide molecule lies in the optimization of the search range, which is often inadequate due to the low degrees of freedom in the initial conformation generated by linking a linear peptide molecule.
Innovation Solution
An initial conformation generation apparatus and method that identifies Cα atoms of amino acid residues, arranges them on a circumference, and adds main and side chains to generate a model, optimizing the search range for stable conformations using a generalized-ensemble method.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If a linear peptide molecule is cyclized by linking head and tail to generate initial conformation, then the cyclic peptide structure is formed, but the degrees of freedom of amino acid residues are reduced leading to inadequate search range
Solution Approach 1:
The patent applies preliminary action by pre-arranging Cα atoms on a circumference before adding main and side chains. This preliminary geometric arrangement ensures that the initial conformation has optimized spatial distribution of atoms, providing adequate search range for stable conformations while maintaining ease of generation through automated modeling.
Solution Approach 2:
The patent changes the parameter of initial conformation generation by arranging Cα atoms on a circumference rather than using traditional linear cyclization. This parameter change increases the degrees of freedom in the initial structure, enabling broader search range for stable conformations while keeping the generation process systematic and automated.
2Device complexity
If traditional linear peptide cyclization method is used, then the generation process is simple, but the initial conformation has low degrees of freedom resulting in missed stable conformations
Solution Approach 1:
The patent performs preliminary arrangement of Cα atoms on a circumference before chain addition, which preliminary establishes an optimized geometric framework. This approach maintains relatively simple generation complexity while significantly improving reliability by ensuring the initial conformation covers adequate conformational space for accurate stable conformation search.
Solution Approach 2:
The patent applies spheroidality by arranging Cα atoms on a circumference (circular geometry) instead of linear arrangement. This curved geometric approach increases the degrees of freedom in the initial conformation, improving the reliability of stable conformation search by preventing missed conformations, while adding only moderate complexity to the generation process.
Data Source
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AI summary
An initial conformation generation apparatus includes a generation unit that generates a model representing a cyclic peptide molecule by identifying Cα atoms of each of a plurality of amino acid residues, by arranging the identified Cα atoms on a circumference, and by adding main chains and side chains of the plurality of amino acid residues; and a search instruction unit that causes a search unit to search for a stable conformation of the cyclic peptide molecule by using the generated model as an initial conformation of the cyclic peptide molecule.