Rosetta and the Design of Ligand Binding Sites.
Proteins that bind small molecules (ligands) can be used as biosensors, signal modulators, and sequestering agents. When naturally occurring proteins for a particular target ligand are not available, artificial proteins can be computationally designed. We present a protocol based on RosettaLigand to redesign an existing protein pocket to bind a target ligand. Starting with a protein structure and the structure of the ligand, Rosetta can optimize both the placement of the ligand in the pocket and the identity and conformation of the surrounding sidechains, yielding proteins that bind the target compound.
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37235, USA.
Rocco
R
Moretti
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Department of Pharmacology, Vanderbilt University, Nashville, TN, 37235, USA.
Brian J
BJ
Bender
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37235, USA.
Brittany
B
Allison
Department of Chemistry, Vanderbilt University, Nashville, TN, 37235, USA. jens@meilerlab.org.|Center for Structural Biology, Vanderbilt University, Nashville, TN, 37235, USA. jens@meilerlab.org.|Department of Pharmacology, Vanderbilt University, Nashville, TN, 37235, USA. jens@meilerlab.org.
Jens
J
Meiler
D001665:Binding Sites; D008024:Ligands; D011506:Proteins / Q000378:metabolism*
D008024:Ligands; D011506:Proteins
Computational design; Ligand docking; Protein design; Protein/small molecule interaction; Sequence optimization