Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions.

ABSTRACT: Understanding how making structural changes in small molecules affects their binding affinities for targeted proteins is central to improving strategies for rational drug design. To assess the effects of varying the nature of nonpolar groups upon binding entropies and enthalpies, we designed and prepared a set of Grb2-SH2 domain ligands, Ac-pTyr-Ac₆c-Asn-(CH₂)_n-R, in which the size and electrostatic nature of R groups at the pTyr+3 site were varied. The complexes of these ligands with the Grb2-SH2 domain were evaluated in a series of studies in which the binding thermodynamics were determined using isothermal titration calorimetry, and binding interactions were examined in crystallographic studies of two different complexes. Notably, adding nonpolar groups

SUBMITTER: Cramer DL 

PROVIDER: S-EPMC7680455 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature