4th EucheMs chemistry congress

Poster Session 1
s872
chem. Listy 106, s587–s1425 (2012)
Poster session 1 - Physical, theoretical chemistry
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exPLorinG the nAture of
CArBohydrAte-AroMAtiC diSPerSion
interACtionS viA SoPhiStiCAted
CoMPutAtionAL CheMiStry tooLS
S. KozMon 1 , r. MAtuSKA 2 , v. SPiwoK 3 , J. KoCA 1
1 CEITEC - Central European Institute of Technology Masaryk
University, Computational Chemistry Group, Brno,
Czech Republic
2 National Centre for Biomolecular Research Masaryk
University, Laboratory of Computational Chemistry, Brno,
Czech Republic
3 Institute of Chemical Technology, Department of Biochemistry
& Microbiology, Praha, Czech Republic
Interactions of saccharides with receptors belong to the most
important ones. The carbohydrates represent signalling molecules
from so-called glycocode, which is recognized by the variety of
proteins. There are several ways how saccharides interact with
proteins. The role of dispersion-driven CH-π interactions in
protein-carbohydrate interactions has been underestimated for a
long time. This type of interaction occurs between carbohydrate
apolar faces and aromatic amino-acids.
We introduce first systematic study of CH-π interactions
between carbohydrates (β-D-glucopyranose, β-D-mannopyranose,
α-L-fucopyranose) and aromatic amino-acid models: benzene and
naphtalene. 3D interaction energy (E ) scan was performed to
int
elucidate interaction energy maps for carbohydrate-benzene
interaction. Resulting stationary complexes were reoptimized and
their E was refined at highly-sophisticated level. To study
int
possible degree of additivity, we used geometries of carbohydratebenzene
complexes to build-up monodentate (interaction with one
CH-group) and bidentate (interaction with two CH-groups)
carbohydrate-naphtalene complexes.
Results show E in carbohydrate-benzene complex up
int
to -5,40 kcal/mol. We localized most attractive regions where the
E is highest. The strongest interaction is localized above and
int
under CH-groups of carbohydrate. Additionally, benzene can
recognize the specific hydrogens of carbohydrate in specific ideal
distance (|(C)H-π| distance around 2,3 ?). The aromatic ring is
coplanar with the carbohydrate cycle.
Localization of the strongest interaction regions for
carbohydrate-benzene complex lead us to idea about possible
additivity of the CH-π interaction. Therefore, E of bidentate
int
carbohydrate-napthalene complexes were analyzed. The
hypothesis of total additivity of the interaction was not confirmed.
However, the E exhibits certain degree of additivity. The E of
int int
bidentate complex forms 2/3 of sum of E of monodentate ones
int
and 4/5 of sum of E of carbohydrate-benzene complexes.
int
Acknowledgement: Financial support by the German Science
Foundation (Di 1517/2-1) is gratefully acknowledged.
This work was supported within the project “CEITEC-Central
European Institute of Technology” (CZ.1.05/1.1.00/02.0068)
from European Regional Development Fund. Access to the
MetaCentrum computing facilities provided under the research
intent MSM6383917201 is acknowledged.
Keywords: carbohydrate; benzene; naphtalene; ab initio
calculations; density functional calculations;
4 th EucheMs chemistry congress
P - 0 0 2 7
deProtonAted G8 And ProtonAted A38 in the
GenerAL ACid/BASe MeChAniSM of the hAirPin
riBozyMe SeLf-CLeAvAGe reACtion PAthwAy
v. MLynSKy 1 , P. BAnAS 1 , n. G. wALter 2 , J. SPoner 3 ,
M. otyePKA 1
1 Regional Centre of Advanced Technologies and Materials,
Department of Physical Chemistry, Palacky University
Olomouc, Czech Republic
2 Department of Chemistry Single Molecule Analysis Group,
University of Michigan, Ann Arbor MI, USA
3 Institute of Biophysics, Academy of Sciences of the
Czech Republic, Brno, Czech Republic
The hairpin ribozyme is a member of the group of
small ribozymes, performing self-cleavage and -ligation without
direct participation of metal ions. Experiments identified two
catalytically active residues, guanine 8 (G8) and adenine
38 (A38), but their exact roles remain still elusive. We carried out
all-atom molecular dynamics (MD) simulations in explicit solvent
on 50-500 ns time scales in order to compare the impact of various
protonation states of G8 and A38. We observed that the
geometries with the canonical G8 and protonated A38H + agreed
well with the crystal structures, while those bearing a
deprotonated G8- and a canonical A38 gradually perturbed the
active site. The geometries generated by MD simulations were
further analyzed by the hybrid quantum-mechanical/molecular
mechanical (QM/MM) method. We calculated energies along the
reaction pathways and indentified activation barriers and
rate-limiting steps. We found three possible reaction scenarios
with activation barriers in good agreement with those derived
from experiment (20-21 kcal/mol). These scenario were:
(i) a general base (deprotonated G8- )/general acid (protonated
A38H + ) mechanism with activation barrier of 20.4 kcal/mol;
(ii) two mechanisms involving a proton shuttle via the
nonbridging oxygen in the presence of canonical G8 together with
either A38 or A38H + (20.5 or 21.0 kcal/mol, respectively); and
(iii) a combined proton shuttle/general acid mechanism with
canonical G8 and protonated A38H + (21.0 kcal/mol). In all cases,
the initial nucleophile attack of the A-1(2'-OH) group on the
scissile phosphate represented the rate-limiting step along the
reaction path. We suggest that RNA self-cleavage may benefit
from several microscopic pathways that are energetically
comparable. Among those pathways, the reaction mechanism with
deprotonated G8- as general base and protonated A38H + as general
acid is the most consistent with the experimentally measured
kinetic pH profiles.
Keywords: Enzyme catalysis; Ribozymes; Cleavage reactions;
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc