Lipid metabolism disorders (including inborn errors of lipid metabolism) are illnesses where trouble occurs in breaking down or synthesizing fats (or fat-like substances). Lipid metabolism disorders are associated with an increase in the concentrations of plasma lipids in the blood such as LDL cholesterol, VLDL, and triglycerides which most commonly lead to cardiovascular diseases.
ChemDiv Virtual Screening Methodology Swiss-Prot Protein Targets and PDB X-Ray Structure Search
Training Sets – ChEMBL 25, PubMed, Current Patent Literature (CAS, Integrity) Machine Learning Data Curation :
a) KNIME/RDKit, kNN classifier, Distance in BitVector Cosine Space, FCFP12 (10,240 bit) fingerprints
b) Hybrid 2D QSAR/Fingerprint Model – Kernel Chemical Classification/Regression (kcc) 3D Shape Similarity Virtual Screening :
APF® MolSoft, Lam et al J. Comp Aided. Mol. Design (2017, 2018 & 2019); APF- Totrov Chem Biol Drug Des. (2008) Structure-Based (Ligands, Fragments, Covalent Fragments) Docking / Virtual Screening :
a) Multiple Receptor Conformation (MRC) 4D Docking; ICM-Pro MolSoft, Bottegoni et al (2009) J. Med. Chem. 52:397
b) Ligand-Biased Ensemble receptor Docking (LigBEnD); ICM-Pro MolSoft, Lam et al J. Comp Aided. Mol. Design (2018) REOS, MedChem & PAINS Filters – Removal of reactive, toxic, promiscuous, and other undesirable structural motifs Diversity Picking (Tanimoto) : RDKit implementation of the MaxMin algorithm – Ashton, M. et. al., Quant. Struct.-Act. Relat., 2002, 21, 598-604.