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APOPTOSIS video (17.11.14)




Když už člověk jednou je, tak má koukat aby byl.
A když kouká, aby byl, a je, tak má být to,
co je, a nemá být to, co není,
jak tomu v mnoha případech je. J. Werich

Did you know? The length of all joined DNA from one adult body (111 mld km) is more as the distance between Earth and Pluto (7.5 mld km)!
Adult human body consists from ca 3.72 x 10E13 cells.
Ann Hum Biol 2013 40 471.
Current lenght of human DNA is ca 3 m.
Length of all joined human DNA from one adult body is:
3.72 x 3 x 10E13 m = 11.16 x 10E10 km = 111 mld km !!!
Earth Neptun distance is 4.4 mld km.
Earth Pluto distance is 7.5 mld km.
The Nature!  (14.02.14)


Počítače a nové lieky: Martin Karplus, Michael Levitt a Arieh Warshel

Martin Karplus  (Harvard University and the University of Strasbourg, France, equiation, CV)

za čo získali NC (opis, opis 2


 FBDD, SanDiego, April 12-14, 2011.

Charles Reynolds, Ansaris: Let Gibbs be Your Guide: Free Energy Simulations in Fragment-Based Drug Design...developed fast free energy method for simulating the interaction of small molecule fragments with their target proteins, as well as computational methodology for linking these fragments into ligands.

Pfizer: X-ray based screening of the proprietary fragment collection Carol Austin, Ph.D., Biology Group Leader, Discovery, Selcia Ltd.:  Screening using Capillary Electrophoresis (CE). Selcia have successfully developed a CE-based method to detect weak fragment binding interactions with soluble protein targets.

Denis Zeyer, Ph.D., CEO, Novalix: Mass Spectrometry in Fragment Library Screening Non-covalent mass spectrometry is a biophysical method that allows detection and characterization of intact protein-compound complexes through accurate mass measurements. Combining high sensitivity and automation, this unique tool is an alternative and/or a complementary screening method compare to NMR or SPR.

Schrodinger: ...importance of accurate tautomer and ionization state prediction....Glide docking can accurately place fragments when induced-fit of the protein is not significant

Isabelle Krimm, University of Lyon: of the advantages to FBDD over high throughput screening is the high hit rates observed in the fragment-based screening campaigns. However, these hit rates may be due to the low specificity of the fragments.

Johnson & Johnson:  ...Our method uses protein crystallography as the sole detection tool for fragment-based lead discovery.  We provide results from our ketohexokinase campaign detailing the progression from initial X-ray based fragment screen to a unique lead series with promising drug-like properties.

Gregg Siegal, ZoBio: ...We have developed a method of biophysical screening that for the first time has enabled FBDD on membrane proteins. The method, TINS, has been applied to two different GPCRs and novel, allosteric modulators have been discovered.


Ligand efficiency as a guide in fragment hit selection and optimization   (2010)
Ligand efficiency (LE): a useful metric for lead selection   (2004)
delta G = -RT.lnKd  (T= 300K), LE = delta G / Nnon-hydrogen = heavy atoms

Fragment-Based Drug Discovery, April 2011, SanDiego, CA, USA X-Ray Based Fragment Screening
Structure-Based Fragment Docking
Virtual Screening
Fragment Screening of Soluble and Membrane Bound Targets
Fragment-Inspired Medicinal Chemistry (Daniel A. Erlanson, Ph.D., Co-Founder, Carmot Therapeutics, Inc.)
Drug Discovery in the Allosteric World

KINASE INHIBITORS, 2011 June 6.-8., Cambridge, MA, USA
Resistance to Kinase Inhibitors
    (Isabelle Dussault, Ph.D., Director, Oncology Research, Amgen)
Non-ATP Competitive Kinase Inhibitors

    (Doriano Fabbro, Ph.D., Head, Kinase Biology, Novartis)
Kinases in Oncology - Hot Targets
Structure-Based Kinase Inhibitor Design

False-positive results, False-negative results