Identification of Cryptic Sites/Interactions using Probe-Based Induction Algorithm (MIST)®

March 23, 2021by kcat

Cryptic pockets are sites on enzymes that only become apparent when ligands (substrate, co-substrate, cofactor) binds. They do not correspond to local minima in the computed conformational free energy landscape of the un-liganded proteins. Hence, they close in all the molecular dynamics simulations performed. Their formation is also known to be an interplay between both the classical mechanisms of induced-fit and conformational selection. At kcat we were able to see interactions that stabilize the attack conformation and transition states which did not appear in n normal simulation.

At kat Enzymatic we use:
Sampling water interfaces through Scaled Hamiltonians (SWISH) (Vladimiras Oleinikovas, 2016)
Fragment-based cryptic site discovery (Dmitri Beglov, 2018)
Kcat’s novel probe-based induction algorithm (MIST)