Solutions to IT problems

Solutions I found when learning new IT stuff

Creating a Framework for Chemical Structure Search – Part 4

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Series Overview

This is Part 4 – Component Selection of the “Creating a Framework for Chemical Structure Search“-Series.

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Finally I will start with the actual creation of the framework. In this part I will introduce the main components (existing 3rd party frameworks and libraries) I use and briefly explain my choices. At this point I think it is fair to mention that my work was basically integrating different existing software components into my desired end-product while taking into account real-world problems and offering a solution for them. There are no new magic algorithms in chemical structure searching, modeling or drug discovery to be found here!

My first try

In my previous effort at creating a framework for chemical structure search, I thought being platform independent, especially regarding the used relational database management system (RDBMS), is an important aspect. Therefore I relied on doing the chemical structure search in the application and not the database. However it is exactly that part that lead to huge performance and efficiency problems. I had to do some stuff that just felt wrong and “hacky” to get usable performance.

Encountered issues with Application-based Substructure Search

Object Creation Performance

The first issue was, that for every structure search, all the structures (molfiles) passing the fingerprint screen had to be loaded from the database and converted to an IAtomContainer Object from the Chemistry Development Kit. It was the creation of these objects that was very CPU intensive. This was due to the fact that you had to detect aromaticity and similar things for every AtomContainer object. I found the solution for this in OrChem, a free cartridge for Oracle based on the CDK. The creators seemed to have the exact same issue and came up with their custom format. That format stored everything required like aromaticity and so forth in a CDK-specific way so the creation of IAtomContainers was not an issue anymore.

Substructure Search Performance

The second issue was the mediocre performance of the substructure search itself. The solution was a complex approach using multi-threading and queues. The first thread screened all structures using the pre-generated fingerprints. Fingerprints were stored in the database but loaded into memory on application start. If a structure passed the screen it’s database id was put into a queue. A second thread reads form that queue, loaded the molfile from database and generated the IAtomContainer and put them into a second queue. Then there were multiple threads (configurable amount) that took the AtomContainers from the queue and did the actual test for subgraph isomorphism. Again, if a structure passed this phase too, it’s database id was put into the output queue and the AtomContainer discarded. This last step was required because AtomContainers are memory hogs and you had to control somehow how many there were in memory at any time.

CPU load now easily reached 100% for seconds during substructure searches. I then realized that the database alone could easily use 20% or more of that probably due to loading all the structures form it. So I added the option to hold the custom format from OrChem in memory ( not big of an issue actually in terms of memory consumption) to reduce load on database and hence use those CPU cycles for substructure search. I guess you have long figured out how convoluted this all was. But it actually worked amazingly well! Because the hits were put into a queue it was easily possible to display the first say 5 hits on a web page while the search continued in the background. So you could give the impression of a very fast search!

Why start from scratch again?

So why change it? Tons of reasons. All of this was done with plain JDBC and various kinds of data transfer objects. Tight-Coupling and maintainability was a serious issue. On the application side of things it was impossible to sort the results because hits are returned somewhat randomly and hence real paging was not possible either. The second thing was how could you search for a substructure and a numeric property at the same time? Well the solution for that was, that one of the substructure search methods had a Set-argument. The Set should contain the database ids of the structures the search should be performed over. Hence do an SQL query for the numeric property first and feed the ids into the substructure search. That worked but again, not very straight forward. Adding and using such custom properties to the database was rather messy too, it lacked proper transaction support and so forth. All in all it was nothing to be proud of and certainly not usable in a real production environment. I did however learn a lot about the Java 5 concurrency package.

Component for Substructure Search

I decided that being dependent on a specific RDBMS is a minor issue compared to above outlined problems. I already knew about the open-source Bingo Cartridge and to my luck the company behind it was developing a version for PostgreSQL. So my choice of this component was easy. Use PostgreSQL with Bingo, both are free and open-source.

Application-side Chemistry toolkit

Especially for Input-output the framework required a Chemistry Toolkit and I again chose the Chemistry Development Kit CDK.


While it would be preferable to be independent of the ORM, I wasn’t able to achieve that but I admit I did not but much effort in it. MoleculeDatabaseFramework uses JPA 2.0 and hibernate as it’s JPA provider. The part that is hibernate specific is the custom SQL dialect I created for accessing the Structure Search functions of Bingo in JPQL and hence also QueryDSL. There is no specific reason I chose hibernate except I already knew it and it was able to do what I required. So I did not investigate any other JPA providers.

Application Framework – Dependency-Injection

Well I guess this is obvious. I chose Spring. I’ve heard and read a lot about Spring. I’ve always wanted to learn it and this was my chance. I also did not want the framework to depend an a full-blown Java EE Application server.

Data Access Layer – CRUD and Querying

I initial started the project with plain Spring and JPA (Hibernate). But shortly after I in my “research” I read about Spring Data JPA and it’s integration with QueryDSL. I quote from Spring-Data website:

Spring Data JPA aims to significantly improve the implementation of data access layers by reducing the effort to the amount that’s actually needed. As a developer you write your repository interfaces, including custom finder methods, and Spring will provide the implementation automatically.

To illustrate this here an example snippet showing an example implementation of my framework:

public interface RegistrationCompoundRepository extends ChemicalCompoundRepository {

    List findByRegNumberStartingWith(String regNumber);


RegistrationCompound has a property called regNumber. Above interface method is automatically implemented by Spring Data and will return a result List of the RegistrationCompounds that match the passed in argument. That’s all you need to write. No SQL and not even a method implementation. Just create the interface and then follow the findBy method conventions of Spring Data.

A Spring Data repository can also make use of QueryDSL.

Querydsl is a framework which enables the construction of type-safe SQL-like queries for multiple backends including JPA, JDO and SQL in Java.


List result = query.from(customer)
    .orderBy(customer.lastName.asc(), customer.firstName.desc())

If you use QueryDSL in your Spring Data Repository using QueryDslPredicateExecutor

@Transactional(propagation = Propagation.MANDATORY)
public interface ChemicalCompoundRepository
        extends ChemicalStructureSearchRepository, JpaRepository<T, Long>,
        QueryDslPredicateExecutor {

the repository will have additional methods that take a QueryDSL Predicate as an input. A Predicate is basically the WHERE-Clause of the query, like from above example"A%"). Some methods take additional parameter like a Pageable. This can be used for paging, the Pageable includes the paging (limit, offset) and sorting information.

This all means it is trivial to extend the repository my framework provides and add your own custom search methods to it. With using predicates you can create complex queries which at the same time search by chemical substructure, return the result sorted and paged and all this with a 1-line method declaration.

public Page findByChemicalStructure(String structureData,
            StructureSearchType searchType,
            Pageable pageable, Predicate predicate);

So I hope this got you interested!


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