Category: 2017

Formate channels play a crucial role in the metabolism of several different kinds of bacteria by bringing about uptake and export of formate ions. The current study investigates the structure, dynamics and ion channel activity of the formate channel FocA from Escherichia coli by employing extensive molecular dynamics (MD) simulations. The channel, known to be pH-sensitive, is modelled under different pH conditions by considering two different protonation states of a histidine residue. The results show that a fall in pH brings about an enhancement of the formate-conducting activity of the channel. The increased conductivity is a consequence of an overall widening of the pore at low pH, with the widening being brought about by movements of a pore-facing helical domain and a loop region. 

A delicate balance of different types of intramolecular interactions makes the folded states of proteins marginally more stable than the unfolded states. Experiments use thermal, chemical, or mechanical stress to perturb the folding equilibrium for examining protein stability and the protein folding process. Elucidation of the mechanism by which chemical denaturants unfold proteins is crucial; this study explores the nature of urea–aromatic interactions relevant in urea-assisted protein denaturation. Free energy profiles corresponding to the unfolding of Trp-cage miniprotein in the presence and absence of urea at three different temperatures demonstrate the distortion of the hydrophobic core to be a crucial step. Exposure of the Trp6 residue to the solvent is found to be favored in the presence of urea. 

An understanding of the determinants of the thermal stability of thermostable proteins is expected
to enable design of enzymes that can be employed in industrial biocatalytic processes carried out at high
temperatures. A major factor that has been proposed to stabilize thermostable proteins is the high occurrence
of salt bridges. The current study employs free energy calculations to elucidate the thermodynamics of the
formation of salt bridge interactions and the temperature dependence, using acetate and methylguanidium ions
as model systems. Three different orientations of the methylguanidinium approaching the carboxylate group
have been considered for obtaining the free energy profiles.

Molecular dynamics (MD) simulations complement experimental structure determination methods like X-ray crystallography and NMR spectroscopy in elucidating macromolecular structure and behaviour. While these experimental techniques are capable of providing reliable structural information, understanding the atomistic details of structure-function relationships of biomolecules is limited. On the other hand, MD simulations are being extensively used to understand molecular processes, structure-function relationships, intramolecular/intermolecular interactions, and so on. 

Human aquaporin 2 (AQP2) from the family of aquaporins assumes great physiological importance, owing to its association with nephrogenic diabetes insipidus (NDI). The present study provides detailed insights into the transport properties of AQP2 with the use of microsecond-scale molecular dynamics simulations, and explains how these channels conduct water molecules while at the same time excluding other molecules. Water transport is seen to be diffusion-limited, with a barrier of only 1.6 kcal mol^− 1, and the channel is more water-permeable than other known aquaporins. A constriction site with a pore-facing phenylalanine and arginine is proposed to serve as a selectivity filter as well as a gate modulating the conductance state of the channel.