Dr. Thana Sutthibutpong
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Molecular dynamics (MD) simulation is a computational technique widely used to study conformational changes of macromolecules. An atomistic molecular dynamics simulations by GROMACS (Abraham et al., 2015) program requires the information from 1) Coordinate files – specifying types of all atoms, type of residues they are in (amino acids for proteins and nucleotides for nucleic acids) and their Cartesian coordinates – 2) topology files – containing set of parameters (so called ‘Force Fields’) describing inter-atomic and inter-molecular interactions, both for covalent bonding and non-covalent interactions, such as Van der Waals and electrostatics – and 3) MD Input files – containing the setup parameters and options for performing a very large number of numerical integrations (500,000 integrations are needed for 1 nanosecond movement of 1 atom!) and the controlled thermostat and barostat, so that a molecular trajectory file – containing positions and velocities of all atoms as functions of time – can be created. The trajectory file is then used for the analysis and biophysical interpretation.
Protein Engineering: Towards the ‘Super’ Enzymes
Thermostability of the enzymes has become a challenge for molecular biologist and biophysicists due to a vast variety of applications in food biotechnologies, biofuels, and etc. Several processes utilizing these enzymes are carried out at a very high temperature (>100 C), which most of the enzymes cannot withstand and end up losing their ability to catalyze the desired chemical reactions.
Enzymes used as an addition to dried or granulated foods should not only possess a high thermostability, but should also retain their activity under acidic environments, as in stomachs. To meet these demands, ‘engineering’ processes on these structures are needed. Under collaborations with experimentalists on cell cultures, enzyme productions, and enzyme mutations from the Protein Research Group, KMUTT, atomistic molecular dynamics (MD) simulations were used to examine the conformations and behaviors of enzymes within varied conditions, such as at different temperatures, pressures and salt concentrations.
Firstly, simulations will be performed on the wildtype, or the original enzyme structure derived from the x-ray crystallography and NMR database, in order to look for ‘hot spots’ regions. At these sensitive regions, correlated motions with the other regions may cause the whole enzyme structure to collapse or ‘denature’, and lose its ability to digest molecules. After that, mutations will be made by altering some critical chemical components of the enzymes to create more interacting sites and not disturbing the existing sites. In order to verify this hypothesis, other series of atomistic MD simulations will be performed to compare the structural properties with the wildtype. Moreover, to elucidate molecular interactions at the catalytic sites and to quantify the catalytic activity, searching for the most suitable binding sites and binding free energy calculations need to be done. Finally, careful predictions for protein engineering processes can be made for laboratory works to reduce time and resource wasting from unconditional tryout-and-error methods.
Abraham, M.J., Murtola, T., Schulz, R., Pall, S., Smith, J.C., Hess, B., and Lindahl, E. (2015). GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2, 19–25.
|1||- Rossitza N. Irobalieva, Jonathan M. Fogg, Daniel J. Catanese, Thana Sutthibutpong, Muyuan Chen, Anna K. Barker, Steven J. Ludtke, Sarah A. Harris, Michael F. Schmid, Wah Chiu and Lynn Zechiedrich, 2015, Structural diversity of supercoiled DNA. Nature Communication, 6, 8440.||2015||Thana Sutthibutpong|
|2||- Thana Sutthibutpong, Sarah A. Harris, Agnes Noy, 2015, Comparison of Molecular Contours for Measuring Writhe in Atomistic Supercoiled DNA. Journal Chemical Theory and Computation, 11(6), pp 2768-2775||2015||Thana Sutthibutpong|
|3||- Ilda D'Annessa, Andrea Coletta, Thana Sutthibutpong, Jonathan S. Mitchell, Giovanni Chillemi, Sarah Harris and Alessandro Desideri, 2014, Simulations of DNA topoisomerase 1B bound to supercoiled DNA reveal changes in the flexibility pattern of the enzyme and a secondary protein-DNA binding site. Nucleic Acids Research, 42, pp 9304äóñ9312.||2014||Thana Sutthibutpong|
|Doctoral||PhD (Physics)||University of Leeds (United Kingdom)||2015|
|Bachelor||BSc (Physics)||Prince of Songkhla University (Thailand)||2010|