Ali Rana Atilgan, atilgan@sabanciuniv.edu
Co-authors: Canan Atilgan
Multiscale Interactions and Dynamical Systems Theme
Non-synonymous single nucleotide polymorphisms within the coding regions of genes giving rise to amino acid
substitutions have shown to alter drastically biological function of proteins. We have developed methods to simply, yet efficiently, characterize the effects of those substitutions on the conformational changes and, therefore,
on the dynamics and function of biological macromolecules [Annual Review of Biophysics, 41, 205 (2012)].
By changing the residue’s physical–chemical characteristics, such as its charge distribution [Journal of Physical
Chemistry B, 116, 7145 (2012)], or playing with the residue and its neighboring micro-environment [Journal
of Chemical Physics, 135, 155102 (2011)], or altering the temperature of the surrounding water body [Journal
of Chemical Physics, 133, 85101 (2010)], we have effectively demonstrated and confirmed with experimental
studies that the turnover rate of an enzyme, or the time scale of ligand release may be altered in a controlled
manner.
Bacteria continuously adapt to their environment, and while doing that, they carry mutations that take place
at critical locations to their function. Random mutations taking place at the gene level may be expressed on
proteins that are vital for the survival of the organism; with natural selection (“natural” referring to the current
environment that may actually be extreme for normal life) these may become permanent. In this talk we
formulate the ways to decipher the structural and dynamical changes induced on a given protein, by mutants
that let the organism carry its normal function while conferring resistance, under the selection pressure induced
by a given antibiotic.