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DE
NOVO PROTEIN DESIGN IN COMPUTATIONAL GENOMICS AND DRUG DISCOVERY Professor Christodoulos A. Floudas |
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Abstract: Proteins serve as vital
components in our cellular makeup and perform many biological functions that
are essential for sustaining life. An
important feature which determines the functionality of a protein is the form
of its three-dimensional structure. Elucidated protein structures can also serve
as templates for the de novo protein design which is of major importance in
structure-based drug design and plays a pivotal role in the scientific
challenge/roadmap: sequence to structure to function. The primary objective
in de novo protein design is to determine the amino acid sequences which are
compatible with specific template backbone structures that may be rigid or
flexible. It is of fundamental importance since it addresses the mapping of
the space of amino acid sequences to known protein folds or
postulated/putative protein folds. It is also of significant practical
importance since it can lead to the improved design of inhibitors, design of
novel sequences with better stability, design of catalytic sites of enzymes,
and drug discovery. The first part of this
presentation will provide a motivation for the de novo protein design problem
with flexible backbone template structures and an overview of the advances
and limitations of the existing approaches. The second part will introduce a
novel two stage prediction approach. The theoretical prediction results for
several peptides and proteins that include variants of Compstatin,
human beta defensin-2, C3a, and gp41 for HIV-1 will be presented. Comparisons
with experimental findings will also be discussed. Components of the
presentation will also be connected with educational and research aspects
relevant to the worldwide and Greek scientific landscape. . |
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