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Creating a Framework for Chemical Structure Search – Part 9

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Series Overview

This is Part 9 – Putting it all together of the “Creating a Framework for Chemical Structure Search“-Series.

Previous posts:


In this final post I’m going to show you a basic Spring MVC 3 Web Application I made based on MoleculeDatabaseFramework.


This Web Application MDFSimpleWebApp lets you

  • import ChemicalCompounds from an SD-File
  • do a chemical substructure search for compounds
  • view the search hits in a paged, tabular fashion
  • view individual search hits
  • download all search hits as SD-File

This is of course only a subset of all the features offered by MoleculeDatabaseFramework but it gives you a general idea how the framework works in terms of writing code and performance.


MDFSimpleWebApp contains 1 ChemicalCompound implementation called SimnpleCompound. It is the most basic possible implementation of ChemicalCompound with no additional properties.

There is also the entity SimpleLot which extends Containable. However it is not yet currently used within the application.

Repository and Service

MoleculeDatabaseFramework requires that you create a repository interface, a repository implementation (for chemical structure searching), a service interface and a service for each of your entities. Hence I created a SimpleCompoundRepository, SimpleCompoundRepositoryImpl, SimpleCompoundService and SimpleCompoundServiceImpl. These classes offer no custom search methods. They just implement all the methods required by the framework. See the Repository- and Service Packages.


This is the controller for SimpleCompound. The controller takes web requests and passes them on the Service Layer, in this case this is SimpleCompoundService, an implementation of ChemicalCompoundService. The controller exposes certain methods from the service like importing of SD-Files, chemical substructure searching or image rendering of chemical structures.

Rendering Images of chemical structures

For displaying chemical compounds I choose the option to dynamically generate images of all chemical structures in the compound. This functionality is also provided by MoleculeDatabaseFramework. Hence the according controller method is very simple:

@RequestMapping(value = "/{compoundId}/render", method = RequestMethod.GET)
public void renderCompound(@PathVariable Long compoundId,
		final HttpServletResponse response,
		@RequestParam(defaultValue = "500") int width,
		@RequestParam(defaultValue = "150") int height) throws IOException {
	try (ServletOutputStream out = response.getOutputStream()) {
		IAtomContainer mol = compoundService.getCdkMolecule(compoundId);
		MoleculeRenderer renderer = new MoleculeRenderer(width, height);
		renderer.renderMolecule(mol, out);

and in a web page you just need to add the according image tag.

JSP with JSTL:

<img src="<c:url value="/compound/${compound.getId()}/render?width=500&height=300"/>" />

Or generated in JavaScript:

var html = <img alt="' + smiles + '" src="/MDFSimpleWebApp/compound/'+ compoundId + '/render" />
// insert image into existing html element

As example here an image of the web page for viewing a compound:

rendering example

Importing SD-File

For uploading a file using Spring MVC 3 I followed this tutorial. I had to create the very simple class FileUploadForm and the controller method is rather simple too:

@RequestMapping(value = "/import", method = RequestMethod.POST)
public String importCompounds(Model model, FileUploadForm fileUploadForm,
		BindingResult result)
		throws IOException {

	if (result.hasErrors()) {
		model.addAttribute("hasError", true);
		model.addAttribute("bindingResult", result);
		return "importCompounds";
	Reader reader = new InputStreamReader(fileUploadForm.getFileData().getInputStream(), "US-ASCII");
	EntityImportResult importResult = compoundService.importSDF(reader, true);

	model.addAttribute("hasError", false);
	model.addAttribute("imported", importResult.getImportedEntities().size());
	model.addAttribute("present", importResult.getEntitiesAlreadyInDatabase().size());
	model.addAttribute(new FileUploadForm());

	return "importCompounds";

Chemical Structure Search

Search Form

The Chemical Structure Search is made up of a page that contains a tool for drawing chemical structures and submitting the search and the actual page for displaying search results. For drawing chemical structures MDFSimpleWebApp initially used the JChemPaint Applet but I recently changed it to JSME, a JavaScript based drawing tool. See below the search form with JSME:

Chemical Structure Search Form

Search Result Page

The search results page relies heavily on AJAX using JQuery and the JQuery plugin datatables. The search hits are displayed in paged fashion using datatables server-side processing and hence only 1 page of results is fetched from the database. The results table contains an image of the chemical structure, the compounds name and its CAS number. Clicking on the image will show a JavaScript alert containing the SMILES String of the given chemical structure.

Search Results Page

For each new page a AJAX request is sent to the server and the according page is returned. Note that the initial load of the page can take a bit longer. This is due to the fact that the total amount of hits is determined (eg. no SQL LIMIT-Clause). This count is cached so that all page requests are as fast. However due to how OFFSET and LIMIT work, the higher the page number, the longer the search takes. So if you have a high number of hits (eg. several thousands) the last page will load slower than the first one. If you want to display search hits 10’000 to 10’004 the database will search up to hit number 10’004 and then return the last 5 hits. However in general you should improve your search if you get so many hits.

After the page is returned from the server, the data must be converted to JSON and in a format expected by datatables. To achieve that I create the helper class JQueryDatatablesPage that contains all the properties that datatables requires and the according getters and setters. JQueryDatatablesPage is then converted to JSON using Jackson 2 ObjectMapper.

@RequestMapping(value = "/search", method = RequestMethod.GET, produces = "application/json")
public @ResponseBody
String search(
		@RequestParam int iDisplayStart,
		@RequestParam int iDisplayLength,
		@RequestParam int sEcho, // for datatables draw count
		@RequestParam String structure) throws IOException {

	int pageNumber = (iDisplayStart + 1) / iDisplayLength;
	PageRequest pageable = new PageRequest(pageNumber, iDisplayLength);
	Page<SimpleCompound> page = compoundService.findByChemicalStructure(structure, StructureSearchType.SUBSTRUCTURE, pageable);
	int iTotalRecords = (int) compoundService.count(null);
	int iTotalDisplayRecords = (int) page.getTotalElements();
	JQueryDatatablesPage<SimpleCompound> dtPage = new JQueryDatatablesPage<>(
			page.getContent(), iTotalRecords, iTotalDisplayRecords,

	String result = toJson(dtPage);
	return result;


private String toJson(JQueryDatatablesPage<?> dt) throws IOException {
	ObjectMapper mapper = new ObjectMapper();
	mapper.registerModule(new Hibernate4Module());
	return mapper.writeValueAsString(dt);

Jackson 2 can deal with circular references if your entities are annotated with

@JsonIdentityInfo(generator=ObjectIdGenerators.IntSequenceGenerator.class, property="@id")

You also need to register the Hibernate4Module to deal with Lazy Collections!

Donwload of Search Hits

You can download search result hits as SD-File by clicking on the Download Hits-Link on the search results page. The browser will display a dialog were you want to save the file. This uses the exportSDF()-method of SimpleCompoundService.

@RequestMapping(value = "/downloadHits", method = RequestMethod.GET)
public void downloadHits(@RequestParam String structure, HttpServletResponse response) throws IOException {

	List<Long> ids = compoundService.findByChemicalStructure(structure, StructureSearchType.SUBSTRUCTURE);
	HashSet<String> properties = new HashSet<>();
	String disposition = "attachment; fileName=searchHits-" + structure + ".sdf";
	response.setHeader("Content-Disposition", disposition);
	ServletOutputStream output = response.getOutputStream();
	OutputStreamWriter writer = new OutputStreamWriter (output);
	compoundService.exportSDF(ids, writer, properties);

Final Words

See below a demo video of a Chemical Substructure Search in MDFSimpleWebApp with a database of 65’000 compounds. The demo runs on a dual-core mobile i5 running Windows 7 32-bit with 4 GB of RAM installed or said otherwise: The hardware is pretty mediocre.

MDFSimpleWebApp is hosted on bitbucket. If you want to try out this application you can go to the download section on bitbucket and download a fully working standalone version for Windows 64-bit including PostgreSQL, the Bingo Cartridge for Chemical Structure Searching, tomcat as servlet container and this web application. Note: This file is 105 MB due to PostgreSQL and tomcat being included.


Written by kienerj

June 6, 2013 at 12:41

Creating a Framework for Chemical Structure Search – Part 6

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Series Overview

This is Part 6 – Data Access Layer of the “Creating a Framework for Chemical Structure Search“-Series.

Previous posts:



In the previous article I introduced the entity model of MoleculeDatabaseFramework. This article will explain the Data Access Layer which uses Spring-Data-JPA with Hibernate and how the Chemical Structure Search methods of the Bingo PostgreSQL Cartridge are exposed to Hibernate and QueryDSL.

How Spring-Data JPA works

Basic functionality

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.

You create a new interface that extends from generic interfaces provided by Spring-Data and represents the repository for an entity. There are different kinds of repository interfaces but the repositories in MoleculeDatabaseFramework all extend JpaRepository. JpaRepository provides CRUD-methods and some retrieval methods for your entity.

Repositories in MoleculeDatabaseFramework also extend QueryDslPredicateExecutor. This adds findOne(predicate) and findAll(predicate) methods. Predicates are basically type-safe WHERE-Clauses.

Custom query methods

Besides the provided methods you can add your custom search methods by following the findBy-method conventions of Spring Data JPA or by annotating a method with @Query were the value of the annotation is either a JPQL Query or native SQL.

Custom Queries providing your own method implementation

In case you have a very complex query that can’t be automatically created by Spring-Data, you can create them yourself.

1. Create Custom Query Interface

To achieve this you need to first create an interface containing the desired query method(s) and annotate it with @NoRepositoryBean:

public interface ChemicalStructureSearchRepository<T> {

    Page<T> findByChemicalStructure(String structureData,
            StructureSearchType searchType,
            Pageable pageable, Predicate predicate,
            String searchOptions,
            PathBuilder<T> pathBuilder);

    Page<T> findBySimilarStructure(String structureData,
            SimilarityType similarityType,
            Double lowerBound, Double upperBound,
            Pageable pageable, Predicate predicate,
            PathBuilder<T> pathBuilder);

This is the Source Code of ChemicalStructureSearchRepository minus JavaDoc comments.

2. Create a repository extending Custom Query interface

As an example below the Source Code for ChemicalCompoundRepository which extends ChemicalStructureSearchRepository:

@Transactional(propagation = Propagation.MANDATORY)
public interface ChemicalCompoundRepository<T extends ChemicalCompound>
        extends ChemicalStructureSearchRepository<T>, JpaRepository<T, Long>,
        QueryDslPredicateExecutor<T> {
    List<T> findByCompositionsPkChemicalStructureId(Long structureId);
    T findByCas(String cas);

    @Query("select c from Containable c where c.chemicalCompound = ?1")
    List<Containable> getContainablesByCompound(ChemicalCompound compound);

3. Create an implementation of your repository

The convention is that the implementation is named after the repository with “Impl” appended, in this case ChemicalCompoundRepositoryImpl. This implementation must only implement your custom methods in this case defined in ChemicalStructureSearchRepository.

public class ChemicalCompoundRepositoryImpl<T extends ChemicalCompound>
        implements ChemicalStructureSearchRepository<T> {

	//...fields and constructors snipped...

    public Page<T> findByChemicalStructure(String structureData,
            StructureSearchType searchType, Pageable pageable,
            Predicate predicate, String searchOptions,
            PathBuilder<T> compoundPathBuilder) {
			//...implementation snipped...

    public Page<T> findBySimilarStructure(String structureData,
            SimilarityType similarityType, Double lowerBound, Double upperBound,
            Pageable pageable, Predicate predicate,
            PathBuilder<T> compoundPathBuilder) {
			//...implementation snipped...

Below an UML Class Diagram that shows the relationships of ChemicalCompoundRepository:

ChemicalCompoundRepository UML

Spring-Data automatically detects the repository implementation and combines all provided and all your custom search methods into one object which you use by calling them from ChemicalCompoundRepository.

Page<T> page = getRepository().findByChemicalStructure(structureData, searchType,
                pageable, predicate, searchOptions, pathBuilder);

Using the Repositories

MoleculeDatabaseFramework provides generic repositories for all entities in the entity model.

Source Code for all Repositories

To make use of a chemical structure search enabled repository you need to extend it using your specific entity implementation and optionally add your custom find methods:

public interface RegistrationCompoundRepository extends ChemicalCompoundRepository<RegistrationCompound> {

    List<RegistrationCompound> findByRegNumberStartingWith(String regNumber);


That’s it!

You can find further information on how to implement entities and repositories in the MoleculeDatabaseFramework Tutorial as this article is meant to show the inner workings of the framework and not how to use it.

Exposing Bingo PostgreSQL Cartridge Methods

This is done by using a custom dialect extending Hibernates PostgreSQL82Dialect:

public class BingoPostgreSQLDialect extends PostgreSQL82Dialect {

    public BingoPostgreSQLDialect() {
         registerFunction("issubstructure", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1  @ (?2, ?3)::bingo.sub"));
         registerFunction("isexactstructure", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1  @ (?2, ?3)::bingo.exact"));
         registerFunction("matchessmarts", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1  @ (?2, ?3)::bingo.smarts"));
         registerFunction("matchesformula", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1  @ (?2, ?3)::bingo.gross"));
         registerFunction("issimilarstructure", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1  @ (?2, ?3, ?4, ?5)::bingo.sim"));
         registerFunction("hasmassbetween", new SQLFunctionTemplate(
                 StandardBasicTypes.BOOLEAN, "?1 > ?2::bingo.mass AND ?1 < ?3::bingo.mass"));         

And as a usage example a source code snippet from ChemicalCompoundRepositoryImpl:

public Page<T> findByChemicalStructure(String structureData,
            StructureSearchType searchType, Pageable pageable,
            Predicate predicate, String searchOptions,
            PathBuilder<T> compoundPathBuilder) {
	BooleanExpression matchesStructureQuery; // this is a Predicate!

	switch (searchType) {
		case EXACT:
			matchesStructureQuery = BooleanTemplate.create(
					"isExactStructure({0},{1},{2}) = true",
			matchesStructureQuery = BooleanTemplate.create(
					"isSubstructure({0},{1},{2}) = true",
		//...snipped other cases

	baseQuery = baseQuery.from(compoundPathBuilder)
			.innerJoin(compound.compositions, composition)
			.innerJoin(, structure)

Full Source Code for ChemicalCompoundRepositoryImpl

The next Part will focus on the Service Layer. The Service Layer controls transactions and security.

Written by kienerj

May 2, 2013 at 07:51

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.

Previous posts:



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!