Drug Active Site Detection Using Pathogenic Mutation Analysis
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Solution Overview
Problem
Current methods lack a suitable approach for identifying drug active sites on proteins, which is essential for drug development, as existing techniques cannot accurately determine the specific sites on a protein's three-dimensional structure where compounds can bind to adjust protein function.
Innovation Solution
A system and method that utilize pathogenic mutation data and three-dimensional protein structure analysis to detect drug active sites by identifying empty spaces adjacent to pathogenic mutations with sufficient volume and connectivity for drug binding, exposed on the protein's surface or accessible through a path.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If binding energy calculation is performed for compounds at any site on the three-dimensional space of the protein, then binding force can be calculated, but it is not possible to select compounds capable of adjusting the protein function because binding strength does not indicate functional activity
Solution Approach 1:
The patent applies local quality by transitioning from uniform binding energy calculation across the entire protein surface to focused analysis at specific local regions identified as pathogenic mutation sites. The method calculates binding energy specifically at locations where pathogenic mutations occur, thereby identifying areas with high functional importance. This localized approach enables differentiation between binding sites that confer functional activity versus those that do not, resolving the contradiction between obtaining binding force data and losing functional activity information.
2Productivity
If virtual screening is performed without knowing the active site, then compound screening can be conducted, but the process is inefficient and inaccurate because compounds binding to non-active sites cannot be distinguished from those binding to active sites
Solution Approach 1:
The patent implements preliminary action by pre-identifying pathogenic mutation sites in the protein structure before conducting virtual screening. The method uses pathogenic mutation data to predict functionally important sites in advance, then focuses the compound screening process on these pre-identified regions. This preliminary identification of active sites enables subsequent virtual screening to be both efficient (by reducing the search space) and accurate (by focusing on functionally relevant locations), thereby resolving the contradiction between productivity and measurement precision.
3Measurement precision
If experimental methods are used to identify active sites, then accurate active site information can be obtained, but the process is time-consuming and applicable only to a minority of proteins
Solution Approach 1:
The patent applies mechanics substitution by replacing experimental methods (mechanical/lab-based) with computational methods (in silico analysis). The method uses pathogenic mutation data and three-dimensional protein structure information to predict active sites through computer-based analysis, eliminating the need for time-consuming experimental procedures. This substitution enables accurate active site identification for a broader range of proteins much faster than experimental approaches, resolving the contradiction between measurement precision and time loss.
Data Source
AI summary
Disclosed herein is a system for discovering a drug active site of protein using a pathogenic mutation. The system includes: a pathogenic mutation position detection unit for detecting a pathogenic mutation position corresponding to a pathogenic mutation in a three-dimensional structure of protein, using pathogenic mutation data containing information on a pathogenic mutation causing an abnormal protein function and protein structure data containing information on the three-dimensional structure corresponding to genetic sequencing of the protein; and a drug active site detection unit detecting a drug active site, corresponding to the pathogenic mutation position, and, to which a drug is bindable.