Close Contact Surface Density for Protein Packing Quality
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Solution Overview
Problem
Current methods for characterizing protein residue packing in the presence of a solvent are limited in providing informative approaches related to thermodynamic properties, such as binding and stability, and fail to quantify packing quality effectively across different residue types.
Innovation Solution
The close contact surface density (CCSD) method calculates the quality of residue packing by determining close contact potentials and contact areas, allowing for the quantification of packing relative to a reference state where inter-residue contacts are replaced by solvent contacts, using a computer-implemented process involving a processor, memory, and clock.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Use of energy by stationary object
If the occluded surface method is used to calculate packing quality, then computational resources are reduced, but the information content and thermodynamic relevance of the results deteriorates
Solution Approach 1:
The patent transforms the packing quality assessment from a purely geometric metric (occluded surface area) to a thermodynamically relevant metric by introducing the close contact surface density that incorporates dispersion interaction energy. This parameter change allows the method to capture both geometric packing and thermodynamic stability without requiring exhaustive computational resources, as the new metric is designed to be computationally efficient while providing deeper physical insight.
2Ease of manufacture
If geometric packing metrics are used, then computational simplicity is maintained, but the ability to predict thermodynamic properties deteriorates
Solution Approach 1:
The patent creates a composite metric that combines geometric packing information (contact surface area) with thermodynamic interaction energy (dispersion forces). This composite close contact surface density metric maintains computational simplicity by using accessible structural data while incorporating physical chemistry principles to predict thermodynamic properties such as binding affinity and stability, thereby achieving both ease of computation and predictive accuracy.
3Adaptability or versatility
If residue-specific packing metrics are developed, then transferability between residue types is improved, but the complexity of the calculation method increases
Solution Approach 1:
The patent develops a universal packing metric that functions across all residue types by focusing on the fundamental physical principle of dispersion interactions rather than residue-specific geometric features. The close contact surface density metric is designed to be applicable to any amino acid residue in any protein context, providing transferable insights into packing quality and thermodynamic stability without requiring separate calculations or parameters for different residue types, thus achieving versatility without excessive complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method enables the comparison of packing quality between different residues and environments, providing insights into thermodynamic processes like binding and folding, and has been shown to correlate with experimental affinity data, aiding in protein engineering and stability assessments.
Implementation Method 1
The CCSD quantity is therefore related to the ubiquitous dispersion interaction (the attractive interaction between atoms), without taking the complex physical dependence into account.
Data Source
AI summary
The invention provides a computer implemented method of quantifying the quality of packing for a residue comprising one or more residue atoms in a first protein in a first conformation, the method comprising: (a) calculating one or more close contact potentials based on a distance between the one or more residue atoms and one or more environment atoms, (b) calculating a contact area of the one or more residue atoms that is exposed to the one or more environment atoms and (c) calculating a close contact surface density (CCSD) by dividing the sum of the one or more close contact potentials by the contact area.