Tomas Bastys

TL;DR: It is proposed that short MAPK‐binding stretches are created in disordered protein segments through a variety of ways and they represent a major resource for ancient signaling enzymes to acquire new regulatory roles.

TL;DR: This study analyzes ten different protease-inhibitor complexes carrying major resistance-associated mutations (RAMs) G48V, I50V, and L90M using molecular dynamics simulations and demonstrates that alchemical free energy calculations can consistently predict the effect of mutations on drug binding.

TL;DR: Estimating the effect of both binding pocket and distant mutations on inhibitor binding free energy using alchemical calculations can reproduce their effect on the experimentally measured I C 50 values indicates valuable insights on interplay between primary and background mutations and mechanisms how they affect inhibitor binding.

TL;DR: It is found that Y823D affects the protein dynamics differently: in the active state, the mutation increases the protein stability, whereas in the inactive state it induces local destabilization, thus shifting the dynamic equilibrium towards the activeState, altering the communication between distant regulatory regions.