Inspiring confidence in computational drug discovery - automated testing for ProtoMS simulations

Posted by s.hettrick on 20 May 2015 - 11:30am

By Devasena Inupakutika, Steve Crouch and Richard Bradshaw

Computer simulations are a good way to study molecular interactions. There have been striking advances in the application of computer simulation to innovative complex systems that have shed light on phenomena across the breadth of modern chemistry, biology, physics and drug design. ProtoMS (short for Prototype Molecular Simulation) is one such major piece of Monte Carlo biomolecular simulation software. The Software Sustainability Institute is working with ProtoMS developers to review and evaluate the software and its code, assess the usability, ease of installation and the long-term sustainability of ProtoMS by collating areas for improvement.

Simulating biomolecules is a particularly challenging problem and requires the use of specific computational techniques to perform experiments or study processes that cannot be investigated by any other methodology. The Essex Research Group of the School of Chemistry at the University of Southampton research innovative applications of simulations to biological systems and focus on the development of new methods and software for biomolecular simulation.

ProtoMS is used to develop new methods to enhance the accuracy and precision of biomolecular simulations, to apply these ideas in the calculation of relative protein/ligand binding free energies and to add new functionalities to computational chemistry programs. The software package consists of Python interface on top of Fortran subroutines. Both GNU and Intel C/C++ and Fortran compilers are supported. Richard Bradshaw and his colleagues from Essex Research Group have been using and improving ProtoMS to develop new science with the aim to replace the time consuming and expensive wet-lab screening of putative drugs with fast and inexpensive computational tools.

To speed up this process as much as possible, the ProtoMS developers have recently introduced automated setup and analysis tools, written tutorials and run workshops so that even novice users can create and run their own computational experiments. However, significant challenges to widening usage of the software remained - for example, how could new users, working with their own hardware and OS environment, be reassured that ProtoMS was reliably installed and giving correct results?

Due to its relevance and use in drug design, pharmaceutical industry partners have expressed interest in exploring and examining the capabilities of ProtoMS simulation methods. With their intention of becoming a more complete software package, making its future development self-sustaining and reaching out to wider community of industry partners and researchers, the Essex Research Group successfully applied to our Open Call.

We will be assisting them in developing an automated test suite to reassure users of performance, and ensure that any newly added features and alterations to the software do not affect other areas of functionality. We also aim to include some profiling of the routines covered by the developed test suite, as details of the test suite coverage will help future developers in identifying gaps/routines that aren’t tested yet, and uses to fill those gaps. This work will also involve checking the preciseness of the test suite results with Intel compilers too.

For more details, please see our who do we work with page, or the publications involving ProtoMS.