MolPort Screening Compound® Phase Database
This document provides an overview of the MolPort Screening Compound Phase database
distributed by Schrödinger. MolPort provides structure files for the screening deck incompressed SDF format. The SDF input is processed to generate structures suitable forproperty calculations and for the generation of the Phase database, as well as for thegeneration of the GPU shape screening bin file.
The structures are run through LigPrep in order to generate stereoisomers, as well as
tautomers and charged states using Epik, including the calculation of metal-binding states. The
LigPrep output is then imported into a Phase database to generate pharmacophore sites,
conformers and fingerprints. Database subsets are provided for drug-like, lead-like, near-drug,and fragment structures. The LigPrep output is also used to generate the bin datafile for GPU
shape screening. Updates to the distribution are provided on a quarterly basis. Included at theend of this document are the commands run to prepare the structures and to generate thePhase database and the shape screening bin file.

Table 1. Structure counts. Some structures are problematic and will not make it through theentire workflow.
Distribution

Count

Source SMI

4,973,086

2D Properties

4,972,412

3D variants

10,274,716

Schrödinger Inc. Report generated 04-01-2024 17:33

Page 1 of 6

Classifications
Schrödinger classifies screening compounds based on properties calculated on a single,neutralized and desalted representation. Near drug-like compounds are those that fall close,
but not quite into the drug-like property space. Drug-like compounds are expected to haveproperties similar to known marketed drugs. Lead-like compounds typically have a more
restrictive set of properties that align with the goals of finding a hit and expanding that hit into a
more drug-like compound. Fragments are compounds that are typically very small and areused to probe a target in order to determine the functionalities expressed by compounds thatbind to a particular site. All other molecular structures are not given a classification.
Several rubrics are used in a hierarchical funnel to associate a molecular entity to a specificclass. Note that even though a molecule may fit into several classifications, in practice,compounds are allowed to match and get assigned to categories further down the funnel in theorder: near drug-like, drug-like, lead-like, to fragment. The count of structures in each class issummarized in table below.
Table 2. Classification criteria. These properties are discussed below. Note that NCC, NR,and HAC correspond to Num chiral centers, Num rings, and Num heavy atoms as calculated byligfilter. Structures are assigned to a class by the last successful match on all criteria
proceeding from right to left.
Near drug-like

Drug-like

Lead-like

Fragment−1.5 ≤ AlogP ≤ 5.5−1 ≤ AlogP ≤ 40 ≤ AlogP ≤ 3

AlogP ≤ 3150 ≤ MW ≤ 575

250 ≤ MW ≤ 500

250 ≤ MW ≤ 375

MW > 110

30 < PSA < 150

50 < PSA < 130

PSA < 110

PSA ≤ 110

HBD ≤ 5

HBD ≤ 5

HBD ≤ 2

HBD ≤ 3

HBA ≤ 12

HBA ≤ 10

HBA ≤ 5

HBA ≤ 5RB ≤ 10RB ≤ 10RB ≤ 10RB ≤ 3

NCC ≤ 3

NCC ≤ 3

NCC ≤ 1
NR ≥ 1
HAC ≤ 18

Table 3. Screening classification
Drug-like

Lead-like

Near drug-like

Fragment

OthersCount

2,193,461

451,568

1,474,451

175,840

677,092Percentage

44.1%

9.1%

29.7%

3.5%

13.6%

Schrödinger Inc. Report generated 04-01-2024 17:33

Page 2 of 6

Database Property Distribution

Schrödinger Inc. Report generated 04-01-2024 17:33

Page 3 of 6

Property Description
A brief description of each property is provided below.
HBD:
Number of hydrogen bond donors
HBA:
Number of hydrogen bond acceptors
RB:
Number of rotatable bonds
Total Rings:
Number of rings
Stereo Centers:
Number of stereogenic centers
N+O:
Sum of nitrogen and oxygen atoms
AlogP:
Logarithm of the atomistic partition coefficient
PSA:
Fragment-based topological polar surface area
MW:
Molecular weight
Frac. CSP3:
Frequency of sp3-hybridized carbon atoms with respect to total carbon atom count

Schrödinger Inc. Report generated 04-01-2024 17:33

Page 4 of 6

Schrödinger commands for creating the database
LIGPREP STRUCTURE PREPARATION$SCHRODINGER/ligprep -epik -bff 16 -s 16 -pht 1.0 -emb -isd Molport_input.sdf.gz -omae
ligprep.mae.gz
SHAPE BIN FILE CREATION$SCHRODINGER/shape_screen_gpu generate -shape_data_treatment remote-shape_data_dir /path/2024q1_shape -source /path/ligprep.mae.gz -flex -shape_type pharm-sample thorough -limit 10 -conformer_format compact
PHASE DATABASE CREATION
Add records to the database$SCHRODINGER/phase_database /path/2024q1_molport.phdb splice ligprep.mae.gz -new-fmt int -title s_lp_Variant -JOB 2024q1_molport_splice
Generate sites, conformers, fingerprints$SCHRODINGER/phase_database /path/2024q1_molport.phdb revise -sites -confs all -fp -adddendritic,fdendritic,maccs,radial,ecfp4 -props -JOB 2024q1_molport_reviseExtract properties$SCHRODINGER/phase_database /path/2024q1_molport.phdb extract -map
Generate subsets-- Drug-like:$SCHRODINGER/phase_database /path/2024q1_molport.phdb query subset_drug_like-where "r_canvas_AlogP >= -1.0 AND r_canvas_AlogP <= 4.0 AND r_canvas_MW >= 250.0
AND r_canvas_MW <= 500.0 AND r_canvas_PSA > 50.0 AND r_canvas_PSA < 130.0 AND
i_canvas_HBD <= 5 AND i_canvas_HBA <= 10 AND i_canvas_RB <= 10 AND
i_canvas_ChiralCenterCount <= 3"-- Near-drug:$SCHRODINGER/phase_database /path/2024q1_molport.phdb query subset_near_drug-where "r_canvas_AlogP >= -1.5 AND r_canvas_AlogP <= 5.5 AND r_canvas_MW >= 150.0
AND r_canvas_MW <= 575.0 AND r_canvas_PSA > 30.0 AND r_canvas_PSA < 150.0 AND
i_canvas_HBD <= 5 AND i_canvas_HBA <= 12 AND i_canvas_RB <= 10 AND
i_canvas_ChiralCenterCount <= 3"-- Lead-like:
Schrödinger Inc. Report generated 04-01-2024 17:33

Page 5 of 6

$SCHRODINGER/phase_database /path/2024q1_molport.phdb query subset_lead_like-where "r_canvas_AlogP >= 0.0 AND r_canvas_AlogP <= 3.0 AND r_canvas_MW >= 250.0
AND r_canvas_MW <= 375.0 AND r_canvas_PSA <= 110.0 AND i_canvas_HBD <= 2 AND
i_canvas_HBA <= 5 AND i_canvas_RB <= 5 AND i_canvas_ChiralCenterCount <= 1"-- Fragment-like:$SCHRODINGER/phase_database /path/2024q1_molport.phdb query subset_fragment-where "r_canvas_AlogP <= 3.0 AND r_canvas_MW > 110.0 AND r_canvas_PSA <= 110.0
AND i_canvas_HBD <= 3 AND i_canvas_HBA <= 5 AND i_canvas_RB <= 3 AND
i_canvas_RingCount >= 1 AND i_canvas_HeavyAtomCount <= 18"-- Epik metal state$SCHRODINGER/phase_database /path/2024q1_molport.phdb query subset_epik_metal_only-where "b_epik_Metal_Only == 0"

Schrödinger Inc. Report generated 04-01-2024 17:33

Page 6 of 6