20 research outputs found
Noncovalent Interactions of Hydrated DNA and RNA Mapped by 2D-IR Spectroscopy
Biomolecules couple to their aqueous environment through a variety of
noncovalent interactions. Local structures at the surface of DNA and RNA are
frequently determined by hydrogen bonds with water molecules, complemented by
non-specific electrostatic and many-body interactions. Structural fluctuations
of the water shell result in fluctuating Coulomb forces on polar and/or ionic
groups of the biomolecular structure and in a breaking and reformation of
hydrogen bonds. Two-dimensional infrared (2D-IR) spectroscopy of vibrational
modes of DNA and RNA gives insight into local hydration geometries, elementary
molecular dynamics, and the mechanisms behind them. In this chapter, recent
results from 2D-IR spectroscopy of native and artificial DNA and RNA are
presented, together with theoretical calculations of molecular couplings and
molecular dynamics simulations. Backbone vibrations of DNA and RNA are
established as sensitive noninvasive probes of the complex behavior of hydrated
helices. The results reveal the femtosecond fluctuation dynamics of the water
shell, the short-range character of Coulomb interactions, and the strength and
fluctuation amplitudes of interfacial electric fields.Comment: To appear as Chapter 8 of Springer Series in Optical Sciences:
Coherent Multidimensional Spectroscopy -- Editors: Cho, Minhaeng (Ed.), 201
Interaction of microtubule depolymerizing agent indanocine with different human αβ tubulin isotypes
Multibody cofactor and substrate molecular recognition in the myo-inositol monophosphatase enzyme.
Molecular recognition is rarely a two-body protein-ligand problem, as it often involves the dynamic interplay of multiple molecules that together control the binding process. Myo-inositol monophosphatase (IMPase), a drug target for bipolar disorder, depends on 3 Mg(2+) ions as cofactor for its catalytic activity. Although the crystallographic pose of the pre-catalytic complex is well characterized, the binding process by which substrate, cofactor and protein cooperate is essentially unknown. Here, we have characterized cofactor and substrate cooperative binding by means of large-scale molecular dynamics. Our study showed the first and second Mg(2+) ions identify the binding pocket with fast kinetics whereas the third ion presents a much higher energy barrier. Substrate binding can occur in cooperation with cofactor, or alone to a binary or ternary cofactor-IMPase complex, although the last scenario occurs several orders of magnitude faster. Our atomic description of the three-body mechanism offers a particularly challenging example of pathway reconstruction, and may prove particularly useful in realistic contexts where water, ions, cofactors or other entities cooperate and modulate the binding process.NF acknowledges support from Generalitat de Catalunya (FI-Agaur). GDF acknowledges support from MINECO (BIO2014-53095-P) and FEDER.We also thank all the volunteers of GPUGRID who donated GPU computing time to the project