אירועים
אירועים והרצאות בפקולטה למדעי המחשב ע"ש הנרי ומרילין טאוב
דימה קוזקוב (אונ' בוסטון)
יום רביעי, 21.03.2012, 13:00
חדר סמינרים, קומה 4, בניין אמרסון, טכניון
Sampling energy landscape of macromolecular interactions is a challenging
problem of computational biology. Classical approaches like Molecular
Dynamics and Monte Carlo are not always optimal for these applications due
to large configurational space of the problem. On contrary The Fast Fourier
Transform (FFT) correlation sampling approach can exhaustively evaluate the
energies of billions of macromolecular configuratins on a grid provided two
limitations - the energy is described in the form of a correlation function
and the interacting molecules are assumed rigid. Here we show that by
removing above restrictions, i.e adding accurate molecular mechanics energy
function and introducing flexibility, FFT based approaches can become method
of choice for the molecular recognition problems.
We present several applications of the FFT based approaches. First is the
problem of protein-protein interactions, where our automatic docking server
ClusPro was top performing server in world wide experiment on blind
assesment of protein interactions (CAPRI). Second is protein hot spot
identification method FTMap, which is computational analogue of NMR or X-ray
based screening using libraries of fragment-sized compounds. Such
experimental approaches include the Multiple Solvent Crystal Structures
method used by Ringe and co-workers, who soaked protein crystals in the
solution of organic solvents, or the experiments by the Fesik group at
Abbott Laboratories, who determined protein-ligand interactions by NMR. In
both methods, it has been observed that the small organic compounds cluster
in the active sites of proteins.The binding of various compounds provides
information on the druggability of the site, and can be used as input for
fragment based drug design. Method is shown to agree well with experiments
and is applied to binding site identification, finding of druggable sites
on protein-protein interactions, transmembrane proteins, and nucleic acids.