IntroductionIn situations where protein X-ray structure or related structures for template-based homology modeling are unavailable for structurebased virtual screening, computational methods for drug design rely principally on ligand-based approaches. Ligand-based approach depends on at least one known active compound; which serves as the query for searching library of compounds using predefined molecular descriptor parameters [1,2]. Three categories of chemical descriptors have been characterized till date; physical properties descriptors (1D-descriptor), molecular topology and pharmacophore descriptors (2D-descriptors) and geometrical descriptors (3D-descriptors, often requires prior knowledge of target protein binding-pocket) [3][4][5]. When there are multiple bioactive compounds for a given target, quantitative structure activity relationships (QSARs) method is more beneficial. QSAR method provides predictive mathematical model for biological activities using statistical clustering of multiple descriptors variables [6,7]. We sought to derive a mathematical equation from minimal set of ligand descriptors for set of Lysophosphatidic acid receptor (LPA1) inhibitors. With this equation, we hope to accurately predict the activity of a test set and hopefully used in ligand-based virtual screening for new high-affinity LPA1 antagonists. Materials and MethodsHere, using Molecular Operating Environment (MOE) [8], multiple descriptors (SlogP (SlogP_VSA0-6), SMR (SMR_VSA0-4), a_acc, ASA, E_stb, a_hyd, and Kier (Kier1-2, KierA1-2)) [8] have been generated for training set of compounds (CHEMBL3819) in order to establish a mathematical equation to model LPA1 inhibition (antagonism). PCA analysis was also conducted to determine the principle components of the equation using scientific vector language (SVL) programming built into the MOE. Results and DiscussionFirst, The IC-50 values of 134 unique entries (LPA1 inhibitors) from ChemBL database (CHEMBL3819) were converted to Gibb's free energy of binding using Cheng-Prusoff equation [9] {Equation1} at S<<