Cyclic Peptide Shape Factor Predicts Cell Membrane Permeability
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Solution Overview
Problem
Designing cyclic peptides with cell membrane permeability above 1000 Da is challenging, and existing methods are inadequate for predicting their permeability, leading to high research costs and limited industrial applications.
Innovation Solution
A method for predicting cell membrane permeability of cyclic peptides using a molecular shape factor r, calculated by Expression (1), which is in the range of 0.4 to 0.6, based on structural information acquired through X-ray crystallography, molecular dynamics calculation, or two-dimensional 1H-NMR measurement, followed by ellipsoidal approximation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a cyclic peptide has a molecular weight of more than 1000 to exhibit specific protein binding properties, then the specific protein binding properties are improved, but the cell membrane permeability deteriorates
Solution Approach 1:
The invention changes the molecular shape parameter (ellipsoidal shape factor) of the cyclic peptide to optimize cell membrane permeability. By controlling the molecular shape factor to be within a specific range (0.4-0.6), the peptide achieves both high molecular weight (>1000 Da) for specific protein binding and sufficient cell membrane permeability, resolving the contradiction between these two properties.
2Device complexity
If existing methods are used to predict cell membrane permeability, then the prediction process is simple, but the prediction accuracy deteriorates
Solution Approach 1:
The invention replaces complex empirical prediction methods with a physics-based computational approach using molecular dynamics simulation and ellipsoidal approximation. This substitution of the prediction mechanism achieves high accuracy in predicting cell membrane permeability while maintaining reasonable computational complexity, as it relies on calculating the molecular shape factor from simulated structural data.
3Adaptability or versatility
If cyclic peptides are designed without prediction methods, then the design process is flexible, but the research costs increase
Solution Approach 1:
The invention performs preliminary prediction of cell membrane permeability using molecular shape factor calculation before actual peptide synthesis and experimentation. This preliminary action allows researchers to identify promising candidates in silico, maintaining design flexibility while significantly reducing the number of costly experimental trials needed, thus lowering overall research costs.
Data Source
AI summary
A method for predicting cell membrane permeability of a cyclic peptide enables versatile design of a cyclic peptide with cell membrane permeability. The method includes a first step of acquiring a structure of the cyclic peptide; a second step of calculating a molecular shape factor r which is calculated by Expression (1) after a step of carrying out an ellipsoidal approximation for obtaining each of axis lengths a, b, and c in a case where an axis length in a longest axis direction of a main chain structure is denoted by a, and axis lengths in two other directions which are orthogonal to a and are orthogonal to each other are denoted by b and c in the structure acquired in the first step; and a third step of determining that the cyclic peptide having the molecular shape factor r in a range of 0.4 to 0.6 has cell membrane permeability.r=2b2+c2a2+b2+c2+a2(1)