System and method for aqueous solubility prediction
AssigneeAccelrys Software Inc.
InventorsAilan Cheng, Kenneth M. Merz, Jr.
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Abstract
The present teachings describe a solubility prediction approach that is based, in part, upon quantitative-structure property relationships (QSPR). In various embodiments, the solubility prediction methodology comprises identifying a reduced descriptor set from which a solubility equation is derived. The descriptors used in the solubility equation are based upon simplified structural and molecular features which facilitate researcher understanding and solubility model refinement. Moreover, the present teachings provide solubility prediction relationships that may be used to rapidly screen large libraries or collections of compounds.
Claims72
A method for solubility determination of at least one candidate compound, the method comprising:
- identifying a plurality of descriptors forming an initial descriptor set wherein each descriptor relates to a property of the candidate compound;
- performing a correlation analysis to identify a plurality of substantially correlated descriptors within the initial descriptor set;
- forming a reduced descriptor set from the initial descriptor set wherein selected correlated descriptors are retained from the plurality of substantially correlated descriptors, and wherein at least one retained descriptor comprises a composite descriptor <HBD>*<HBA> wherein <HBD> is a descriptor representing the number of hydrogen bond donors in the candidate compound and <HBA> is a descriptor representing the number of hydrogen bond acceptors in the candidate compound;
- identifying solubility information and descriptor values associated with the reduced descriptor set for a plurality of known compounds forming a training data set;
- identifying a solubility equation based on a selected subset of descriptors contained in the reduced descriptor set and derived using the solubility information and descriptor values for the plurality of known compounds contained in the training data set;
- and
- applying the solubility equation to the descriptor information for the at least one candidate compound to thereby determine the solubility for the at least one candidate compound.
A method for solubility prediction comprising:
- selecting a first plurality of descriptors comprising identifiable compound properties and characteristics;
- forming a correlated descriptor subset from the first plurality of descriptors wherein the correlated descriptor subset comprises selected descriptors identified by correlation analysis, and wherein at least one selected descriptor comprises a composite descriptor <HBD>*<HBA> wherein <HBD> is a descriptor representing the number of hydrogen bond donors in a compound and <HBA> is a descriptor representing the number of hydrogen bond acceptors in a compound;
- generating a solubility prediction function comprising selected descriptors from the correlated descriptor subset identified by statistical analysis of the correlated descriptor subset using a training data set;
- and
- applying the solubility prediction function to predict a compound's solubility on the basis of descriptor information for the compound.
A method for descriptor construction to be used in solubility analysis applications, the method comprising:
- selecting a compound or molecular structure;
- determining the number of hydrogen bond donors <HBD> in the selected compound or molecular structure;
- determining the number of hydrogen bond acceptors <HBA> in the selected compound or molecular structure;
- determining the product of the number of hydrogen bond donors and the number of hydrogen bond acceptors <HBD>*<HBA>;
- and
- associating the product of the number of hydrogen bond donors and the number of hydrogen bond acceptors <HBD>*<HBA> with a first solubility descriptor for the selected compound or molecular structure.
A system for assessing the solubility of at least one compound, the system comprising:
- a descriptor identification component that identifies a plurality of descriptors describing properties and characteristics for the at least one compound;
- a correlation analysis component that evaluates correlations between the plurality of descriptors to identify correlated descriptor groups and further identifies at least one selected descriptor to represent one or more of the correlated descriptor groups, wherein at least one identified descriptor comprises a composite descriptor <HBD>*<HBA> wherein <HBD> is a descriptor representing the number of hydrogen bond donors in a compound and <HBA> is a descriptor representing the number of hydrogen bond acceptors in a compound;
- and
- a solubility modeling component that uses the at least one selected descriptor to form a solubility prediction equation using a training data set for which solubility and selected descriptor information is known.
A method of predicting the solubility of a compound in a solvent, the method comprising:
- counting the number of hydrogen bond donors in each molecule of said compound;
- counting the number of hydrogen bond acceptors in each molecule of said compound;
- multiplying said counts to produce a descriptor value;
- multiplying said descriptor value by a scaling factor to produce a first term of an equation;
- and
- adding said term to other terms of said equation to produce a predicted solubility value.
A computer readable medium having stored thereon instructions which cause a general purpose computer to perform a method of generating a predicted solubility value for a selected compound, said method comprising:
- counting the number of hydrogen bond donors in each molecule of said compound;
- counting the number of hydrogen bond acceptors in each molecule of said compound;
- multiplying said counts to produce a descriptor value;
- multiplying said descriptor value by a constant to produce a first term of an equation;
- and
- adding said term to other terms of said equation.
Dependencies are inferred from the claim text.