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1. The Strength of NH---S Hydrogen Bonds
in Methionine Residues Revealed by Gas
Phase IR/UV Spectroscopy
Himansu S. Biswal*#†, Eric Gloaguen#, Yohan
Loquais#, Benjamin Tardivel# and Michel Mons*#
# CEA, Laboratoire Francis
Perrin, DSM/IRAMIS/SPAM, Bât 522, 91191 Gif-sur-
Yvette, France
# CNRS, Laboratoire Francis Perrin, URA 2453, 91191
Gif-sur-Yvette, France.
† National Institute of Science Education and Research,
Sachivalaya Marg, Bhubaneswar - 751 005, India.
J. Phys. Chem. Lett. 2012, 3, 755 -759 1

2. Motivation
Studies on intermolecular complexes suggest “sulfur” is a potential H-
bond acceptor as “Oxygen”.1
The intramolecular H-bonds frequently observed in proteins such as
Namide-H···S hydrogen bonds linking the sulfur atom of methionine to
backbone NamideH groups has not yet been received much attention.
Open Question
How strong is the Namide-H···S H-bond?
Does it compete with other intramolecular H-bonds found in peptides
and proteins?
How does it control the peptide structure and conformational space?
1Biswal,H. S. et al. J. Phys. Chem. A, 2009, 113, 12763; ibid, 2010, 114, 5497; J. Chem. Phys.
2011, 135, 134306.
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3. Model Peptide and H-bond Pattern
O H O
N H
H3C N N
H
H O
S
H3C
Ac-Phe-Met-NH2 (FM)
CH3
S
O H O
N H
H3C N N
H
H O
Ac-Met-Phe-NH2 (MF)
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4. Experimental Strategy
Pulsed valve
• Laser desorption: hot species in the
gas phase
• Cooling in the supersonic expansion :
Sample molecules are trapped in one or more
(Peptide + graphite) conformations
Vacuum chamber
• Recognition of H-bond network by
IR and UV spectroscopy
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5. IR Spectra and Structure Assignment
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6. Evidence of strong NH---S H-Bonds
The „sulfur‟ atom of Methionine forms both intra and
inter-residue N-H---S H-bond.
intra-residue It is observed from Protein Data Bank 24% Methionine
residues displays such local folding pattern.
inter-residue
Stabilization Energy = 10 kJ/mol
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7. Comparison with Protein Structures
Protein with
-Met - Phe – Sequence
… comparable with
isolated structure
Ramachandran Angles
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8. Conclusions
The sulfur atom of methionine is found to be an H-bond Authors
acceptor as strong as the oxygen atom of backbone
carbonyl groups, despite its less electronegativity
(generally considered as a weaker H-bond acceptor).
The close similarity of local folding of the model
dipeptides and those of proteins suggest that the strong
N-H•••S H-bonds acting in dipeptides also occur in Himansu S. Biswal Eric Gloaguen
proteins. This observation also suggests that they take
part in the local shaping of the protein chain, like the
classical N-H•••O interactions, and illustrates the
relevance of such gas phase data to biochemical issues.
The concept of „Sulfur Center Hydrogen Bonds‟
(SCHBs) needs a proper attention while designing new
generation force field for protein structure simulation. Michel Mons
Acknowledgments
This work was financially supported by the French
National Research Agency (ANR) (Grant ANR-08-BLAN-
0158-01) and the “Triangle de la Physique” Foundation
(Grant 2008-053T-SERPBIO).
Yohan Loquais Benjamin Tardivel
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