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<DIV>
<P class=MsoNormal><SPAN
style="FONT-SIZE: 10pt; COLOR: blue; FONT-FAMILY: 'Arial','sans-serif'"> </SPAN><SPAN
style="FONT-FAMILY: 'Tahoma','sans-serif'"><o:p></o:p></SPAN></P></DIV>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN
style="FONT-SIZE: 18pt; COLOR: black; FONT-FAMILY: 'Verdana','sans-serif'">VABILO
NA INŠTITUTSKO PREDAVANJE /<o:p></o:p></SPAN></P>
<P class=MsoTitle style="MARGIN: 0cm 0cm 0pt; TEXT-ALIGN: center"
align=center><SPAN
style="FONT-SIZE: 18pt; COLOR: black; FONT-FAMILY: 'Verdana','sans-serif'"> INVITATION
TO THE INSTITUTE LECTURE<o:p></o:p></SPAN></P>
<P class=MsoNormal><SPAN lang=FR
style="FONT-SIZE: 8pt"><o:p> </o:p></SPAN></P>
<P class=MsoNormal
style="MARGIN-TOP: 6pt; LINE-HEIGHT: 150%; TEXT-ALIGN: center"
align=center><B><SPAN lang=EN-GB
style="FONT-SIZE: 20pt; LINE-HEIGHT: 150%; FONT-FAMILY: 'Verdana','sans-serif'">Prof.
Arieh Warshel<o:p></o:p></SPAN></B></P>
<P class=MsoNormal style="LINE-HEIGHT: 150%; TEXT-ALIGN: center"
align=center><B><SPAN lang=EN-GB
style="COLOR: black; FONT-FAMILY: 'Verdana','sans-serif'">Department of
Chemistry, </SPAN></B><B><SPAN lang=EN-GB
style="FONT-FAMILY: 'Verdana','sans-serif'"><ns0:place><ns0:PlaceType><SPAN
style="COLOR: black">University</SPAN></ns0:PlaceType><SPAN
style="COLOR: black"> of </SPAN><ns0:PlaceName><SPAN
style="COLOR: black">Southern California</SPAN></ns0:PlaceName></ns0:place><SPAN
style="COLOR: black"><o:p></o:p></SPAN></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN
style="FONT-SIZE: 8pt; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN
style="FONT-SIZE: 8pt; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN
style="FONT-SIZE: 16pt; FONT-FAMILY: 'Verdana','sans-serif'">Četrtek/ Thursday
24. 05. 2007, ob / at 13:00<o:p></o:p></SPAN></B></P>
<H6 style="TEXT-ALIGN: center" align=center><SPAN lang=EN-GB
style="FONT-SIZE: 14pt; FONT-FAMILY: 'Verdana','sans-serif'">Velika predavalnica
Kemijskega inštituta /<o:p></o:p></SPAN></H6>
<H6 style="TEXT-ALIGN: center" align=center><SPAN lang=EN-GB
style="FONT-SIZE: 14pt; FONT-FAMILY: 'Verdana','sans-serif'">Lecture Hall at the
National Institute of Chemistry<o:p></o:p></SPAN></H6>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN
style="FONT-SIZE: 14pt; FONT-FAMILY: 'Verdana','sans-serif'">Hajdrihova 19,
Ljubljana</SPAN><I> <SPAN lang=FR><o:p></o:p></SPAN></I></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN lang=EN-GB
style="FONT-SIZE: 16pt; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN lang=EN-GB
style="FONT-SIZE: 8pt; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN lang=EN-GB
style="FONT-SIZE: 14pt; COLOR: #993366; FONT-FAMILY: 'Verdana','sans-serif'">Looking
for key factors in enzyme catalysis; <o:p></o:p></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN lang=EN-GB
style="FONT-SIZE: 14pt; COLOR: #993366; FONT-FAMILY: 'Verdana','sans-serif'">Some
Recent Confirmation of the Electrostatic idea<o:p></o:p></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN lang=EN-GB
style="FONT-SIZE: 8pt; COLOR: #993366; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></B></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><B><SPAN lang=EN-GB
style="COLOR: #993366; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></B></P>
<P class=MsoBodyText
style="MARGIN-BOTTOM: 6pt; MARGIN-LEFT: 0cm; MARGIN-RIGHT: 0cm; TEXT-ALIGN: justify; mso-margin-top-alt: 0cm"><SPAN
lang=EN-GB style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">Biological
systems were optimized by evolution to reach a maximum overall efficiency.
However, the available structural, spectroscopical, and biochemical
<ns0:PersonName>info</ns0:PersonName>rmation do not allow one to determine what
are the most important catalytic mechanisms. A significant part of this
difficulty is associated with the ill-defined nature of some proposals and with
the slow realization that computer simulation approaches provide perhaps the
best way for defining and examining the issues in a unique way (1-3). This
talk focuses on examination of several proposals including the dynamical
proposal and, idea that correlated motions play a key role in catalysis and the
relationship between KIE and catalysis. A wide range of simulation techniques
are used to examine the magnitude of the dynamical effects. It is found
that these effects do not contribute to catalysis, regardless of the definition
used (2). Next, it is illustrated that enzymes work by using their preorganized
polar environment to stabilize the transition state of the reacting substrates.
This is demonstrated by analyzing the effects of mutations in DHFR (4), which
has been used as an evidence for the importance of dynamical effects. Additional
demonstration is provided by analyzing the preorganization effect in KSI (5) ,
which provided perhaps the best example of the key role of the preorganization
effect.<o:p></o:p></SPAN></P>
<P class=MsoNormal><B><U><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">References:<o:p></o:p></SPAN></U></B></P>
<P class=MsoNormal style="MARGIN-LEFT: 45pt"><B><U><SPAN lang=FR
style="FONT-FAMILY: 'Arial','sans-serif'"><o:p><SPAN
style="TEXT-DECORATION: none"> </SPAN></o:p></SPAN></U></B></P>
<P class=MsoNormal style="TEXT-INDENT: -18pt"><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">1)</SPAN><SPAN
lang=FR style="FONT-SIZE: 7pt"> </SPAN><SPAN
lang=FR style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">Computer
Simulations of Chemical Reactions in Enzymes and Solutions, A. Warshel, John
Wiley & Sons, (1991).<o:p></o:p></SPAN></P>
<P class=MsoBodyTextIndent2
style="MARGIN: 0cm 0cm 0pt; TEXT-INDENT: -18pt"><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">2)</SPAN><SPAN
lang=FR style="FONT-SIZE: 7pt"> </SPAN><SPAN
lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'"> Dynamical
Contributions to Enzyme Catalysis: Critical Tests of A Popular Hypothesis; M. H.
M. Olsson, W. W. Parson and A. Warshel, Chem. Rev. ,106,1737-1756
(2006).<o:p></o:p></SPAN></P>
<P class=MsoBodyTextIndent2
style="MARGIN: 0cm 0cm 0pt; TEXT-INDENT: -18pt"><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">3)</SPAN><SPAN
lang=FR style="FONT-SIZE: 7pt"> </SPAN><SPAN
lang=FR style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">Electrostatic
Basis for Enzyme Catalysis; A. Warshel, P. K. Sharma, M. Kato, Y. Xiang, H. Liu,
and M. H. M. Olsson, Chem. Rev., 106,3210-3235 (2006).<o:p></o:p></SPAN></P>
<P class=MsoBodyTextIndent2
style="MARGIN: 0cm 0cm 0pt; TEXT-INDENT: -18pt"><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">4)</SPAN><SPAN
lang=FR style="FONT-SIZE: 7pt"> </SPAN><SPAN
lang=FR style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">The Catalytic
Effect of Dihydrofolate Reductase and its mutants is determined by
Reorganization Energies Hanbin Liu and Arieh Warshel, Biochemistry
(ASAP).<o:p></o:p></SPAN></P>
<P class=MsoBodyTextIndent2
style="MARGIN: 0cm 0cm 0pt; TEXT-INDENT: -18pt"><SPAN lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'">5)</SPAN><SPAN
lang=FR style="FONT-SIZE: 7pt"> </SPAN><SPAN
lang=FR
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Arial','sans-serif'"> Electrostatic
Contributions to Binding of Transition State Analogues Can Be Very Different
from the Corresponding Contributions to Catalysis: Phenolates Binding to the
Oxyanion Hole of Ketosteroid Isomerase , A. Warshel, P. K. Sharma, Z. T.
Chu and J. Aqvist ,Biochemistry 46, 1466-1476
(2007).<o:p></o:p></SPAN></P>
<P class=MsoBodyText
style="MARGIN-BOTTOM: 6pt; MARGIN-LEFT: 0cm; MARGIN-RIGHT: 0cm; TEXT-ALIGN: justify; mso-margin-top-alt: 0cm"><SPAN
lang=EN-GB
style="FONT-SIZE: 11pt; FONT-FAMILY: 'Verdana','sans-serif'"><o:p> </o:p></SPAN></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN lang=FR
style="FONT-FAMILY: 'Verdana','sans-serif'">Kindly
invited!</SPAN><o:p></o:p></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center> <o:p></o:p></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center><SPAN lang=FR
style="FONT-FAMILY: 'Verdana','sans-serif'">Information: <A
href="mailto:janez.mavri@ki.si">janez.mavri@ki.si</A><o:p></o:p></SPAN></P>
<P class=MsoNormal style="TEXT-ALIGN: center" align=center> <SPAN lang=FR
style="FONT-FAMILY: 'Verdana','sans-serif'"><o:p></o:p></SPAN></P>
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