Computation of electrostatic complements to proteins: a case of charge stabilized binding.
Recent evidence suggests that the net effect of electrostatics is generally to destabilize protein binding due to large desolvation penalties. A novel method for computing ligand-charge distributions that optimize the tradeoff between ligand desolvation penalty and favorable interactions with a binding site has been applied to a model for barnase. The result is a ligand-charge distribution with a favorable electrostatic contribution to binding due, in part, to ligand point charges whose direct interaction with the binding site is unfavorable, but which make strong intra-molecular interactions that are uncloaked on binding and thus act to lessen the ligand desolvation penalty.
Chong
L T
LT
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139-4307, USA.
Dempster
S E
SE
Hendsch
Z S
ZS
Lee
L P
LP
Tidor
B
B
D001426:Bacterial Proteins; D001665:Binding Sites; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012260:Ribonucleases / Q000737:chemistry; D055672:Static Electricity
D001426:Bacterial Proteins; D008024:Ligands; D011506:Proteins; D011956:Receptors, Cell Surface; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease