Chunky Monkey GIST/GLIDE
Maestro 2016-3
Glide 7.2
Amber 16
AmberTools 16
cpptraj-GIST
GISTPP
Glide default ligand pose generation
GlideSP scoring function
Maximum number of ligand poses=5
VDW scaling factor=0.8
Glide Default ligand sampling
Amber 14SB FF
TIP3P Water Model
Amber heavy atom restrainst 2.5 kcal/A^2
All 102 ligands were docked to each of the four prepared structures using GLIDE SP with default parameters. The top score for each ligand was used as the base score for that ligand.
Ligands for each target structure were given a solvent displacement score generated from a GIST scoring functional. The parameters for this functional were from the energy only scoring function (Table 1 of dx.doi.org/10.1021/ct401110x). This functional gave a flat score of kcal/mol for displacing water in regions where water has a high density and unfavorable energy compared to bulk. Water was considered to be displaced from a voxel (a cubical region with sides of length 0.5 angstroms) if any heavy atom of the ligand was within 3.0 angstroms of the voxel center.
Ligands were rescored for each target structure independently. Displacement scores were calculated for each target. The average of these scores was calculated and substracted from the score for each ligand indivually. Thus, the average GIST solvent displacement score for each target was zero. If the average absolute water contribution was greater than 15% of the total GLIDE score then the contribution was scaled to be 15% of the average total GLIDE score.
The final score for each ligand pose was the sum of the original GLIDE score and the rescored water correction term described above.
Chunky Monkey Gist
Maestro 2016-3
Glide 7.2
pH 7.4
Tautomers considered
OPLS2005 Forcefield
The work for this submission has been performed by the following people:
Steven Ramsey, Tom Kurtzman; Lehman College of CUNY
Emilio Gallicchio; Brooklyn College of CUNY
Lauren Wickstrom; Borough of Manhattan Community College of CUNY
Identification of Target Structures - To address the significant loop and helical reorganization, A subset of four protein structures from the 36 provided were identified to be used for docking. These four (structure ids: hgaf, nqqw, hqmf, fggu) were chosen by first grouping ligands into four groups (+1 outlier group) with common core features and picking a representative structure from each group.
Each of the four structures was protonated with the ligand and crystallographic water molecules in place using Maestro's prepwizard with default parameter settings. Protonation states were visually inspected with particular attention paid to HIS, ASN, and GLN. HIS451 and 298 protonation states and/or flip state were modified in each of the four structures to best maintain local hydrogen bond contacts.
Ligprep was used to prepare the ligands with
all default settings except that core positions were maintained.
Glide default ligand pose generation
GlideSP scoring function
Maximum number of ligand poses=5
VDW scaling factor=0.8
Glide Default ligand sampling
All 102 ligands were docked to each of the four structures using GLIDE SP with default parameters. The top score for each ligand was used for this submission.