News & Reports
Report for the 2014 University of Melbourne Selby Research Award: Dr Lars Goerigk
Quantum chemical optimization of DNA structures and related compounds
1. Summary and outcomes
The aim of this project was to develop a methodology that allows the efficient structural optimisation of large biomolecules with quantum-chemical procedures. One particular aim was to develop this optimiser for DNA structures with the potential to be used to complement the standard X-ray crystallographic macromolecular refinement technique, which is a key step in a crystallographic structure determination.
Very early during this project it became necessary to modify the original aim and instead of DNA, the project initially dealt with protein structures. The reason for this was that protein crystal structures can usually be obtained at much higher resolutions and therefore they serve as a much better benchmark to assess the applicability of the newly developed optimiser. This part of the project was carried out successfully in collaboration with Prof. Jeffrey Reimers (Shanghai University, China) and A/Prof. Charles A. Collyer (The University of Sydney) and it resulted in a publication in December 2014 (reference 1 in the publications list at the end of this document). This paper deals with protein optimisation and quantum refinement and we demonstrated that standard optimisation techniques are not adequate in this area and that they are outperformed by a newer approach presented in the publication. Its peer-reviewers received the publication very well and they shared our hopes that it can have an important impact on the quantum-chemistry community. The results of this paper were also presented at the National Congress of the Royal Australian Chemical Institute in Adelaide in December 2014. This study forms an important basis for the next step of the project, which is a similar investigation on common structural features of DNA. This work is currently in progress. The outcomes can then be transferred to existing crystal structures of various forms of DNA, e.g. B-DNA, Z-DNA or G-DNA.
As I had arrived at the University only a couple of weeks prior to the award of the Selby Research Award, the provided funds were crucial in building a functioning research infrastructure. This infrastructure helped me not only with my main project, but it was highly beneficial in establishing four collaborations with other researchers that have all resulted in publications. In all cases, funding from the Selby Scientific Foundation has been appropriately acknowledged. My collaboration with Dr. Amir Karton (The University of Western Australia) on the quantum-chemical treatment of barrier heights of pericyclic reactions showed surprisingly large errors for some popular quantum-chemical protocols, and the editors of the Journal of Computational Chemistry acknowledged the importance of our study by featuring it as a front-cover article (reference 2). This paper was also the eighth most-read of this journal in February 2015.
Two separate collaborations with experimentalists Dr. Chris Ritchie and Prof. Evan Bieske – both from the School of Chemistry – have also resulted in recently published articles (references 3 and 4). A paper written in collaboration with Dr. Bun Chan and Prof. Leo Radom (The University of Sydney) has been accepted for publication in the Journal of Computational Chemistry and we hope that it will be featured as a front-cover article (reference 5).
In summary, the past months have been very successful. Further publications are planned and also in those the Selby Research Award will be acknowledged. Finally, I would like to thank the Selby Scientific
Foundation for supporting my research and for laying the foundation of a flourishing research environment that will also guarantee success in my future projects.
2. Statement on the spent budget
A large portion of the awarded $15,000 were spent for computer hardware, i.e. an Apple MacPro as a local workstation for quantum-chemical calculations and an Apple iMac as a workstation to access high- performance computer clusters in Melbourne and in Canberra (total costs $7,672). The Selby Award also allowed me to support an international visiting student from the Indian Institute of Technology Roorkee, who worked with me for seven weeks from November 2014 until January 2015 (combined cost of $3,573.57). Publication costs for the front-cover article in the Journal of Computational Chemistry were USD 495 (about $640.5). As of 3 June 2015, there are still $3,113 left, which will be spent until the end of July 2015, i.e. until the end of my 12th month after having been granted the Selby Award. This money will be spent for conference registration to PACIFICHEM 2015 in Hawaii – as outlined in my award application – and for the expected front-cover publication costs of reference 5. Also, as the already purchased hardware turned out to be less expensive than anticipated at the time of my grant application, I am able to purchase additional hardware that will guarantee the continuation of this successful project.