Research
We are a newly established research group at Fatih University, department of physics. The focus of our research is to explore theoretical and computational topics pertaining to biophysics. The central theme is the application and development of the computer and modeling methods to describe structure and dynamics of biomolecular machines, especially those that interact with DNA, as well as several families of anti-cancer drug molecules (e.g. comphotetcin) that are involved in DNA-protein interactions. The biomolecules are mainly represented at the atomic level, while electronic descriptions of the active/important regions are also included via QM/MM methodology. The large-scale atomistic/dynamical calculations are coupled with the electronic structure calculations on the small anti-cancer drug molecules. The purpose for the quantum level calculations is to explore structure-function relations of these small molecules, with the help of information gained from the large-scale dynamical simulations.
DNA-Topoisomerase Systems
The central focus of research in our group is the Topoisomerase - DNA interactions. It is well known that topology of DNA is crucial in many cellular processes as well as for the stability and confinement of the DNA in the cell. The topology of DNA is defined by a geometry independent topological parameter, the linking number (Lk), which specifies the number of helices that the two DNA strand cross each other.The proteins that cut one or both strands of the DNA, and therefore bring changes in the topology of the DNA, are called 'topoisomerases' (in short, topos). They are ubiquitous enzymes which are essential for the cellular regulations of DNA supercoiling caused by the processes such as replication, transcription, and recombination. These proteins also adjust the steady-state level of DNA supercoiling in order to facilitate protein-DNA interactions. The main research here is the applications of three major physical theories on mechanics, namely quantum, classical, and statistical, in a harmonious blend to focus on different aspects of the dynamic mechanism of the DNA-Topoisomerase and DNA-Topoisomerase-Anticancer molecular systems.
Human topoisomerase I is one of the most important one among topos, as it functions as a swivel in DNA replication, RNA transcription, and chromosome condensation/segregation. Therefore, it is also the sole target of many anti-cancer drug molecules. What you see on the left, and also on the main page of the physics department, is the relaxation of a positively supercoiled DNA by human topoisomerase I. The movie is obtained via the application of molecular mechanical methods, as the equations of motions are solved on a supercomputer (pc-clusters). To read more, and to see more movies on this system, refer to our recent paper that can be obtained freely from NAR website (click here for the paper)
Other than Human Topoisomerase I, our research includes DNA gyrase, S. cerevisiae topoisomerase II & E-coli topoisomerase IV (Type 2A), E.coli topoisomerase I ve III (Type 1A), and Human Topo II Beta. Comptothecin, etoposide, and mitoxantrone family anti-cancer organic molecules are also a focus of research as they target the actions of topos.