Entropy-enthalpy transduction caused by conformational shifts can obscure the forces driving protein-ligand binding.

ABSTRACT: Molecular dynamics simulations of unprecedented duration now can provide new insights into biomolecular mechanisms. Analysis of a 1-ms molecular dynamics simulation of the small protein bovine pancreatic trypsin inhibitor reveals that its main conformations have different thermodynamic profiles and that perturbation of a single geometric variable, such as a torsion angle or interresidue distance, can select for occupancy of one or another conformational state. These results establish the basis for a mechanism that we term entropy-enthalpy transduction (EET), in which the thermodynamic character of a local perturbation, such as enthalpic binding of a small molecule, is camouflaged by the thermodynamics of a global conformational change induced by the perturbation, such as a switch into a hi

SUBMITTER: Fenley AT 

PROVIDER: S-EPMC3523842 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature