Scientific Imagination to Predictions to Medical Discoveries

"I am enough of an artist to draw freely upon my imagination. Imagination is more important than knowledge. Knowledge is limited. Imagination encircles the world." - Albert Einstein

"Omnium artium medicina nobilissima est." Hippocrates, the "father" of modern Medicine

 

Imagining how SUR.x and Kir6.x may interact with each other and nucleotides plus drugs to open and close KATP led Babenko et al to the depicted ABCC/KCNJ gating model validated by Babenko and others. It was predicted and then demonstrated that the non-canonical TMD1-5 (TMD0-L0) of SUR.x couples with Kir6.x and controls the open channel probability, and that the benzoido moiety of the WHO-recommended essential drug, glibenclamide, is close to the L0 and the Kir N-terminus absent in frozen, including sub-nm-resolution macrocrystallographic homologous, structures.


 

Based on Dr. Babenko's multi-template 3D homology models, canonical SUR cores (shown as four gray masses, each consisting of TMD1-NBD1-TMD2-NBD2) are dockable to the (TMD0-L0/Kir6)4 mini-KATP part of KATP complex in two distinct ways. Subsequent electron microscopy images of KATP indicated which one to choose.

  

Dr. Babenko generated the first electrophysiologically meaningful system for molecular dynamics simulation (MDS) of intrinsically hyperactive (delN32Kir6.2delC35)4 in a phospholipid bilayer patch, in a cube of 140 mM aqueous solution. The 0.1 ns-frame of his MDS clip shows the free energy-minimized system viewed from the cytoplasmic side of the Kir, with potassium ions shown as green spheres. Steered MDS at the Pacific Northwest National Laboratory or other super-computing centers might improve our knowledge of K+ selective conduction. But the ultimate biophysical understanding of mechanism in Kir, KATP, and other membrane transport protein systems shall come from the superlative, RF/EU-built, femtosecond-fast Euro-XFEL, allowing to see how these bionanomachines operate under quasi-physiological conditions.

  

Dr. Babenko created the first composite model of (SUR2A/Kir6.2)4 for the "ATP Vingt Ans apres" Volume of JMCC, hoping that Ångström-resolution structures of KATP isoforms will be obtained before the twentieth anniversary of the truly heroic cloning of SUR1 by the Bryan Team  to enable the atomic structure-guided design of novel SUR isoform-selective ligands for treatment of several diseases.


Dr. Babenko can share his next predictions with α sponsor who knows what Dr. Einstein said after being denied tenure [drag the mouse "The pursuit of truth and beauty is a sphere of activity in which we are permitted to remain children all our lives"] and what another free genius, Jean-Paul Sartre, wrote declining the Prize which others but not Russians write anything for.

 

So, ergo, darum, donc, поэтому... continue exploring BabenkoLabs' Web Pages