  Small molecules are often found to exhibit extraordinarily diverse biological
activities. Metformin is one of them. It is widely used as anti-diabetic drug
for type-two diabetes. In addition to that, metformin hydrochloride shows
anti-tumour activities and increases the survival rate of patients suffering
from certain types of cancer namely colorectal, breast, pancreas and prostate
cancer. However, theoretical studies of structure and dynamics of metformin
have not yet been fully explored. In this work, we investigate the
characteristic structural and dynamical features of three mono-protonated forms
of metformin hydrochloride with the help of experiments, quantum chemical
calculations and atomistic molecular dynamics simulations. We validate our
force field by comparing simulation results to that of the experimental
findings. Nevertheless, we discover that the non-planar tautomeric form is the
most stable. Metformin forms strong hydrogen bonds with surrounding water
molecules and its solvation dynamics show unique features. Because of an
extended positive charge distribution, metformin possesses features of being a
permanent cationic partner toward several targets. We study its interaction and
binding ability with DNA using UV spectroscopy, circular dichroism, fluorimetry
and metadynamics simulation. We find a non-intercalating mode of interaction.
Metformin feasibly forms a minor/major groove-bound state within a few tens of
nanoseconds, preferably with AT rich domains. A significant decrease in the
free-energy of binding is observed when it binds to a minor groove of DNA.
