Transcript Document

Intelligent design of Biomimetics (Synzymes):
(Salen)Mn(III) Compound as a Nonpeptidyl mimic of Catalase
R
R
N
N
Mn
X
O
X
O
Cl
Y
2H2O2
Y
Catalase
An incomplete list of possible
treatment applications:
Alzheimer’s disease
Stroke
Heart disease
Aging
Cancer (reduction of the side
effects, allowing higher drug doses
to be administered)
2H2O + O2
Substituents change enzymatic activity:
the biomimetic can be tuned structurally and electronically
GTP
GAP
RAS
QM part: 45 atoms
MM part: 1608 atoms
collected in 483 EFs
~ 40 Å
Potential energy surface for the GTP hydrolysis for the RAS/GAP complex model
(calculated at the B3LYP/4-31G*/3-21G level)
Reaction
path
34
32
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
0
2.0
2.5
3.0
3.5
1.8
2.0
2.2
2.4
2.6
2.8
3.0
3.2
3.4
3.6
3.8
Characterization of Ping-Pong Mechanism for
Dismutation of H2O2 Molecule by (Salen)Mn(III)
Mechanism-Based Structural Tuning of Catalase Activity
of Salen-Manganese Complexes for R=OMe substituted
compound
Abashkin, Burt Inorg. Chem., 2005;
Abashkin, Burt Phys. Chem. B, 2004
Estimated computer resources needed for the exhaustive tuning :
50-60 (substituted biomimetics) x
200-400 (hours of large CPU) = YEARS
Dramatic increase in computation power is needed to solve the
problem
Computational assistance in developing
novel biological nanodevices:
“Simple” Nanoprobe for detecting biowarfare reagents and genetic diseases.
DNA/RNA Target
Recognizer
Recognizer
Fluorescein
Green Light
Target
Practical development of Nanoprobe needs optimization of various elements:
Target
Recognizer
Recognizer
Fluorophores
Linker
Polyethylenglycol (PEG) tether
Rod
Computational support includes QM ( hundreds of atoms)
and MM (thousands of atoms) calculations and/or complex
QM/MM simulations
Feasible only on a supercomputer
Epidermal Growth Factor Receptor Pathway
Dendrimers
Dendrimers
Large number of micro-environments with different properties
Gold Nanoparticles
Gold Nanoparticles
Buckyball (left)
500 atoms
3000 electrons
Gold Particle
3000 to 30000 atoms
500,000 electrons
Problem grows as Ne2