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<p class=MsoNormal><font size=3 face="Times New Roman"><span style='font-size:
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</div>
<p class=MsoTitle style='mso-margin-top-alt:0cm;margin-right:-32.4pt;
margin-bottom:0cm;margin-left:-18.0pt;margin-bottom:.0001pt'><b><font size=5
color=black face=Verdana><span style='font-size:18.0pt;font-family:Verdana;
color:black;font-weight:normal'>VABILO NA INŠTITUTSKO PREDAVANJE /<o:p></o:p></span></font></b></p>
<p class=MsoTitle style='margin-left:0cm'><b><font size=5 color=black
face=Verdana><span style='font-size:18.0pt;font-family:Verdana;color:black;
font-weight:normal'> INVITATION TO THE INSTITUTE LECTURE<o:p></o:p></span></font></b></p>
<p class=MsoNormal><b><font size=3 face=Verdana><span style='font-size:12.0pt;
font-family:Verdana;font-weight:bold'><o:p> </o:p></span></font></b></p>
<p class=MsoNormal><b><font size=3 face=Verdana><span style='font-size:12.0pt;
font-family:Verdana;font-weight:bold'><o:p> </o:p></span></font></b></p>
<p class=MsoNormal align=center style='text-align:center'><b><font size=5
face=Verdana><span style='font-size:20.0pt;font-family:Verdana;font-weight:
bold'>Prof. Dr. Anna Tramontano<o:p></o:p></span></font></b></p>
<p class=MsoNormal align=center style='text-align:center'><font size=1
face=Verdana><span lang=IT style='font-size:8.0pt;font-family:Verdana'><o:p> </o:p></span></font></p>
<p class=MsoNormal align=center style='text-align:center'><font size=3
face=Verdana><span style='font-size:12.0pt;font-family:Verdana'>Department of
Biochemical Sciences "Rossi Fanelli", University of Rome "La
Sapienza", P.le Aldo Moro, 5, Rome, Italy</span></font><font size=3
face=Verdana><span lang=IT style='font-size:12.0pt;font-family:Verdana'><o:p></o:p></span></font></p>
<p class=MsoNormal align=center style='text-align:center'><font size=2
face=Arial><span lang=IT style='font-size:11.0pt;font-family:Arial'><o:p> </o:p></span></font></p>
<p class=MsoNormal align=center style='text-align:center'><font size=1
face=Verdana><span lang=IT style='font-size:8.0pt;font-family:Verdana'><o:p> </o:p></span></font></p>
<p class=MsoNormal align=center style='margin-right:-14.2pt;text-align:center;
line-height:150%'><b><font size=5 face=Verdana><span style='font-size:16.0pt;
line-height:150%;font-family:Verdana;font-weight:bold'>Četrtek / Thursday, 3.
6. 2010, ob / at 13:00<o:p></o:p></span></font></b></p>
<h6><font size=2 face=Verdana><span style='font-size:11.0pt;font-family:Verdana'>Velika
predavalnica Kemijskega inštituta / Lecture Hall at the <o:p></o:p></span></font></h6>
<h6><font size=2 face=Verdana><span style='font-size:11.0pt;font-family:Verdana'>National
<st1:PlaceType w:st="on">Institute</st1:PlaceType> of <st1:PlaceName w:st="on">Chemistry</st1:PlaceName>;
Hajdrihova 19, <st1:City w:st="on"><st1:place w:st="on">Ljubljana</st1:place></st1:City>
<o:p></o:p></span></font></h6>
<p class=MsoNormal style='text-align:justify'><b><font size=4 color="#993366"
face=Verdana><span lang=EN-GB style='font-size:14.0pt;font-family:Verdana;
color:#993366;font-weight:bold'><o:p> </o:p></span></font></b></p>
<p class=MsoNormal align=center style='text-align:center'><a name="OLE_LINK3"></a><a
name="OLE_LINK4"></a><b><font size=5 color="#993366" face=Verdana><span
lang=EN-GB style='font-size:18.0pt;font-family:Verdana;color:#993366;
font-weight:bold'>From Genomes to Proteins and Back</span></font></b><b><font
size=5 color="#993366" face=Verdana><span lang=EN-GB style='font-size:18.0pt;
font-family:Verdana;color:#993366;font-weight:bold'><o:p></o:p></span></font></b></p>
<p class=MsoNormal><u><font size=1 face="Times New Roman"><span lang=EN-GB
style='font-size:8.0pt'><o:p><span style='text-decoration:none'> </span></o:p></span></font></u></p>
<p class=MsoNormal style='text-align:justify'><b><font size=2
face="Times New Roman"><span lang=EN-GB style='font-size:10.0pt;font-weight:
bold'><o:p> </o:p></span></font></b></p>
<p class=MsoNormal style='text-align:justify;text-autospace:none'><font size=2
face=Arial><span style='font-size:10.0pt;font-family:Arial'>The knowledge of
the amino acid sequence of a gene product is still not sufficient to understand
its function at the molecular level: the function of a protein is determined by
and large by its three-dimensional structure.<o:p></o:p></span></font></p>
<p class=MsoNormal style='text-align:justify;text-indent:35.45pt;text-autospace:
none'><font size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>We
can predict the structure of a protein from its amino acid sequence in some
cases, not in all cases. In other words, we cannot, as of today and probably
for some years to come, simulate the folding process of a protein. The only
reason we can continue to discuss the problem of structure prediction is indeed
that proteins are a product of evolution. The evolutionary mechanisms imply
that proteins mostly evolved via small sequence variation, usually single amino
acid substitutions, insertions and deletions. Therefore the sequences of
proteins that are "sufficiently" closely evolutionary related in
evolution preserve detectable similarities. An unfolded polypeptide is
risky for the cell, because it exposes hydrophobic groups that favour
aggregation with other proteins. Consequently, we can assume that each of the
evolutionary steps has produced a structure compatible with the function of the
protein. Note that function is usually brought about by few key amino acids,
but is dependent on their correct positioning in the active site, that is on
the correct folding of the polypeptide.<o:p></o:p></span></font></p>
<p class=MsoNormal style='text-align:justify;text-indent:35.45pt;text-autospace:
none'><font size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>All
the above implies that evolutionary related proteins not only have similar
sequences but also similar structures. In other words, if two proteins have a
sequence sufficiently similar to guarantee that they are evolutionary related,
we might be reasonably certain that they also have a similar structure. This
observation forms the basis of a protein structure prediction method called
"comparative modelling" or "modelling by homology" that we
applied to the human gene product set.<o:p></o:p></span></font></p>
<p class=MsoNormal style='text-align:justify;text-indent:35.45pt;text-autospace:
none'><font size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>We
analysed the putative structure of all the gene products of known structure or
for which a reliable three-dimensional model could be built and analysed the
results asking the question of whether these products could give raise to a
functional element. The most striking results of our analysis is that, for more
than half of these alternative transcripts, the resulting protein structure is
likely to be substantially altered in relation to that of the principal
sequence.<o:p></o:p></span></font></p>
<p class=MsoNormal style='text-align:justify;text-indent:35.45pt;text-autospace:
none'><font size=2 face=Arial><span style='font-size:10.0pt;font-family:Arial'>Our
results leave open two important questions, namely which is the role of the
putative non-functional variants and, equally importantly, how can we reconcile
the number of functions of a human organism with its apparently very low coding
content.<o:p></o:p></span></font></p>
<p class=MsoNormal style='text-align:justify'><font size=1 face=Arial><span
lang=EN-US style='font-size:8.0pt;font-family:Arial'><o:p> </o:p></span></font></p>
<p class=MsoNormal align=center style='text-align:center'><font size=3
face=Arial><span lang=EN-US style='font-size:12.0pt;font-family:Arial'>Vljudno
vabljeni! / Kindly invited!<o:p></o:p></span></font></p>
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color=navy face=Arial><span lang=FR style='font-size:10.0pt;font-family:Arial;
color:navy'><o:p> </o:p></span></font></p>
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