jp6b02732_si_001.pdf (1.73 MB)
Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins
journal contribution
posted on 2016-04-19, 00:00 authored by Pranab Deb, Tapas Haldar, Somnath M Kashid, Subhrashis Banerjee, Suman Chakrabarty, Sayan BagchiNoncovalent interactions,
in particular the hydrogen bonds and
nonspecific long-range electrostatic interactions are fundamental
to biomolecular functions. A molecular understanding of the local
electrostatic environment, consistently for both specific (hydrogen-bonding)
and nonspecific electrostatic (local polarity) interactions, is essential
for a detailed understanding of these processes. Vibrational Stark
Effect (VSE) has proven to be an extremely useful method to measure
the local electric field using infrared spectroscopy of carbonyl and
nitrile based probes. The nitrile chemical group would be an ideal
choice because of its absorption in an infrared spectral window transparent
to biomolecules, ease of site-specific incorporation into proteins,
and common occurrence as a substituent in various drug molecules.
However, the inability of VSE to describe the dependence of IR frequency
on electric field for hydrogen-bonded nitriles to date has severely
limited nitrile’s utility to probe the noncovalent interactions.
In this work, using infrared spectroscopy and atomistic molecular
dynamics simulations, we have reported for the first time a linear
correlation between nitrile frequencies and electric fields in a wide
range of hydrogen-bonding environments that may bridge the existing
gap between VSE and H-bonding interactions. We have demonstrated the
robustness of this field-frequency correlation for both aromatic nitriles
and sulfur-based nitriles in a wide range of molecules of varying
size and compactness, including small molecules in complex solvation
environments, an amino acid, disordered peptides, and structured proteins.
This correlation, when coupled to VSE, can be used to quantify noncovalent
interactions, specific or nonspecific, in a consistent manner.