@article {43841,
	title = {Hidden electrostatic basis of dynamic allostery in a PDZ domain},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {114},
	year = {2017},
	month = {JUL},
	pages = {E5825-E5834},
	type = {Article},
	abstract = {Allosteric effect implies ligand binding at one site leading to structural and/or dynamical changes at a distant site. PDZ domains are classic examples of dynamic allostery without conformational changes, where distal side-chain dynamics is modulated on ligand binding and the origin has been attributed to entropic effects. In this work, we unearth the energetic basis of the observed dynamic allostery in a PDZ3 domain protein using molecular dynamics simulations. We demonstrate that electrostatic interaction provides a highly sensitive yardstick to probe the allosteric modulation in contrast to the traditionally used structure-based parameters. There is a significant population shift in the hydrogen-bonded network and salt bridges involving side chains on ligand binding. The ligand creates a local energetic perturbation that propagates in the form of dominolike changes in interresidue interaction pattern. There are significant changes in the nature of specific interactions (nonpolar/polar) between interresidue contacts and accompanied side-chain reorientations that drive the major redistribution of energy. Interestingly, this internal redistribution and rewiring of side-chain interactions led to large cancellations resulting in small change in the overall enthalpy of the protein, thus making it difficult to detect experimentally. In contrast to the prevailing focus on the entropic or dynamic effects, we show that the internal redistribution and population shift in specific electrostatic interactions drive the allosteric modulation in the PDZ3 domain protein.},
	doi = {10.1073/pnas.1705311114},
	author = {Kumawat, Amit and Chakrabarty, Suman}
}
@article {48171,
	title = {How far is {\textquoteleft}{\textquoteleft}Bulk Water{\textquoteright}{\textquoteright} from interfaces? depends on the nature of the surface and what we measure},
	journal = {Journal of Physical Chemistry B},
	volume = {126},
	year = {2022},
	month = {FEB},
	pages = {1125-1135},
	type = {Article},
	abstract = {<p>
	Using systematic molecular dynamics (MD) simulations, we revisit the question: At what distance from an interface do the properties of {\textquoteleft}{\textquoteleft}bulk water{\textquoteright}{\textquoteright} get recovered? We have considered three different kinds of interfaces: nonpolar (hydrophobic; isooctane-water interface), charged (negative; AOT bilayer), and polar (zwitterionic; POPC bilayer). In order to interrogate the extent of perturbation of the interfacial water molecules as a function of the distance from the interface, we utilize a diverse range of structural and dynamical parameters. To capture the structural perturbations, we look into local density (translational order), local tetrahedral order parameter, and dipolar orientation of the water molecules. We also explore the anisotropic diffusion of the water molecules in the direction perpendicular to the interface as well as the planar diffusion parallel to the interface in a distance dependent manner. In addition, the orientational time correlation functions have been computed to understand the extent of slowdown in the rotational dynamics. As expected, the electrostatic field emanating from the charged AOT interface seems to have the highest long-range effect on the orientational order and dynamics of the water molecules, whereas specific interactions like hydrogen bonding and electrostatic interaction lead to significant trapping and kinetic slowdown for both AOT and POPC (zwitterionic) very close to the interface. Our analysis highlights that not only the length-scale of perturbation depends on the nature of the interfaces and specific interactions but also the type of water property that we measure/calculate. Different water properties seem to have widely different length-scale of perturbation. Orientational order parameters seem to be perturbed to a much longer length-scale as compared to translational order parameters. The global orientational order of water can be perturbed even up to similar to 4-5 nm near the negatively charged AOT surface in the absence of any extra electrolyte. This observation has significant implication toward the interpretation of experimental measurements as well since different spectroscopic techniques would probe different parameters or water properties with possible mutual disagreement and inconsistency between different types of measurements. Thus, our study provides a broader and unifying perspective toward the aspect of {\textquoteleft}{\textquoteleft}context dependent{\textquoteright}{\textquoteright} structural and dynamical perturbation of {\textquoteleft}{\textquoteleft}interfacial water{\textquoteright}{\textquoteright}.</p>
},
	issn = {1520-6106},
	doi = {10.1021/acs.jpcb.1c08603},
	author = {Hande, Vrushali R. and Chakrabarty, Suman}
}
