Modeling the chemical composition of a biological cell wall

Abstract

Techniques are described for determining the strain on a cell wall using two models: 1) a short timescale model, describing the relationship between physical properties assumed to be fixed and 2) a long timescale model, describing the dynamic chemical composition of a cell wall. Short term modeling of the physical properties in a cell wall is used to properly understand how physical factors such as osmotic pressure affects the strain on the cell wall, which is in turn used to identify conditions under which a cell wall will cease to function properly or lyse entirely. Although temporally the physical properties which cause cell walls to underperform/lyse can be evaluated under a short time frame, the chemical properties that lead to the physical properties which cause that behavior themselves change over much longer timescales, in a relative sense.

What is claimed is: 
     
         1 . A method for improving efficiency of drug discovery, the method comprising:
 accessing a statistical model configured to predict information about a molecular composition of a cell wall of a cell based on a plurality of chemical reactions;   accessing initial quantities of a set of input molecules that are reactants for the chemical reactions;   evaluating the statistical model with the initial quantities of the set of input molecules to determine a change in the molecular composition of the cell wall;   determining a set of physical properties for the cell wall based on the change in the molecular composition of the cell wall;   accessing a physics-based model configured to predict a physical integrity of the cell wall;   evaluating the physics-based model based on the physical properties of the cell wall to determine a strain on the cell wall;   responsive to the strain indicating a threshold strain, detecting one or more failure conditions, the failure conditions representing lysis of the cell; and   facilitating a drug discovery process using the detection of the one or more failure conditions, wherein the facilitation includes identifying a drug-discovery target.   
     
     
         2 . The method of  claim 1 , wherein the statistical model describes the relationship between the molecular composition of the cell wall and the physical properties of the cell wall. 
     
     
         3 . The method of  claim 1 , wherein the molecular composition of the cell wall comprises at least one of:
 a number of cross-links between proteins of the cell wall;   a chain length describing a number of molecules in the cell wall;   a mass of the cell wall; and   a thickness of the cell wall.   
     
     
         4 . The method of  claim 1 , wherein the molecular composition of the cell wall comprises at least one of:
 presence of one or more molecules in the cell wall; and   physical arrangement of one or more chemical constituents in the cell wall.   
     
     
         5 . The method of  claim 1 , wherein the statistical model is generated by experimentally varying the molecular composition of the cell wall and measuring the resulting physical properties. 
     
     
         6 . The method of  claim 1 , wherein evaluating the statistical model with the initial quantities of the set of input molecules to determine the change in the molecular composition of the cell wall comprises:
 accessing one or more chemical reactions occurring within the cell wall;   integrating a set of outputs of the statistical model into the molecular composition of the cell wall using the chemical reactions to determine the change in the molecular composition of the cell wall.   
     
     
         7 . The method of  claim 6 , further comprising:
 classifying the chemical reactions into one of a plurality of reaction lists representing a class of reactant molecules; and   integrating a set of outputs of the statistical model into the molecular composition of the cell wall using the chemical reactions to determine the change in the molecular composition of the cell wall is further based on the lists associated with the chemical reactions.   
     
     
         8 . The method of  claim 1 , wherein evaluating the statistical model with the initial quantities of the set of input molecules to determine the change in the molecular composition of the cell wall comprises:
 executing a stoichiometric mass balance model;   performing a flux-based analysis;   solving an ordinary differential equation;   solving a partial differential equation; or   performing a Monte Carlo simulation.   
     
     
         9 . The method of  claim 1 , wherein determining the physical properties of the cell wall is further based on at least one of:
 measurements by one or more mechanical sensors;   data from a live cell, the data including a molecular composition of the cell wall and physical properties of the cell wall; and   data from a live cell, the data including observations of changes in live cell geometry in fluids of different osmolarities.   
     
     
         10 . The method of  claim 1 , wherein the one or more failure conditions comprise:
 a rupture in the cell wall;   a hole in the cell wall;   an inability of the cell wall to grow; and   a death of the cell.   
     
     
         11 . The method of  claim 1 , wherein the physics-based model describes the relationship between the physical properties of the cell wall. 
     
     
         12 . The method of  claim 1 , wherein the physics-based model assumes steady-state conditions within the cell. 
     
     
         13 . The method of  claim 1 , wherein the physics-based model specifies one of the following cell geometries:
 a cylinder;   a cylinder with spherical caps;   a sphere; and   an ellipsoid.   
     
     
         14 . The method of  claim 1 , wherein the physics-based model that relates values for the physical properties for the cell wall determined based on the change in molecular composition of the cell wall to at least one output physical property. 
     
     
         15 . The method of  claim 14 , wherein the physics-based model is further based on:
 values for a set of fixed physical properties unaffected by the molecular composition of the cell wall.   
     
     
         16 . The method of  claim 14 , wherein the physics-based approximates one or more output physical properties comprising:
 turgor pressure;   osmotic pressure;   mechanical stress;   mechanical strain; and   cell geometry.   
     
     
         17 . The method of  claim 14 , wherein the physics-based model further comprises a set of stability criteria, the set of stability criteria describing conditions beyond which a cell experiences failure conditions. 
     
     
         18 . The method of  claim 17 , wherein the set of stability criteria comprises a threshold osmotic pressure beyond which the chemical bonds of the cell wall break. 
     
     
         19 . A non-transitory computer readable storage medium storing instructions that, when executed by a processor, cause the processor to perform a set of actions for improving efficiency of drug discovery, the set of actions comprising:
 accessing a statistical model configured to predict information about a molecular composition of a cell wall of a cell based on a plurality of chemical reactions;   accessing initial quantities of a set of input molecules that are reactants for the chemical reactions;   evaluating the statistical model with the initial quantities of the set of input molecules to determine a change in the molecular composition of the cell wall;   determining a set of physical properties for the cell wall based on the change in the molecular composition of the cell wall;   accessing a physics-based model configured to predict a physical integrity of the cell wall;   evaluating the physics-based model based on the physical properties of the cell wall to determine a strain on the cell wall;   responsive to the strain indicating a threshold strain, detecting one or more failure conditions, the failure conditions representing lysis of the cell; and   facilitating a drug discovery process using the detection of the one or more failure conditions, wherein the facilitation includes identifying a drug-discovery target.   
     
     
         20 . The non-transitory computer readable storage medium of  claim 19 , wherein evaluating the statistical model with the initial quantities of the set of input molecules to determine the change in the molecular composition of the cell wall comprises:
 accessing one or more chemical reactions occurring within the cell wall;   integrating a set of outputs of the long timescale model into the molecular composition of the cell wall using the chemical reactions to determine the change in the molecular composition of the cell wall.   
     
     
         21 . A system comprising:
 a processor; and   a non-transitory computer readable storage medium storing instructions that, when executed by a processor, cause the processor to perform a set of actions for improving efficiency of drug discovery, the set of actions comprising:
 accessing a statistical model configured to predict information about a molecular composition of a cell wall of a cell based on a plurality of chemical reactions; 
 accessing initial quantities of a set of input molecules that are reactants for the chemical reactions; 
 evaluating the statistical model with the initial quantities of the set of input molecules to determine a change in the molecular composition of the cell wall; 
 determining a set of physical properties for the cell wall based on the change in the molecular composition of the cell wall; 
 accessing a physics-based model configured to predict a physical integrity of the cell wall; 
 evaluating the physics-based model based on the physical properties of the cell wall to determine a strain on the cell wall; 
 responsive to the strain indicating a threshold strain, detecting one or more failure conditions, the failure conditions representing lysis of the cell; and 
 facilitating a drug discovery process using the detection of the one or more failure conditions, wherein the facilitation includes identifying a drug-discovery target.