<p> Supporting Information</p><p>Combining Molecular Dynamics Simulation And Ligand-Receptor Contacts</p><p>Analysis As A New Approach For Pharmcophore Modeling: Beta-Secretase 1</p><p>And Check Point Kinase 1 As Case Studies</p><p>Ma'mon M. Hatmala, Shadi Jaberb, Mutasem O. Tahac* </p><p> aDepartment of Medical Laboratory Sciences, Faculty of Allied Health Sciences, The </p><p>Hashemite University, Zarqa, Jordan</p><p> bDepartment of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Zar-</p><p> qa Private University, Zarqa, Jordan</p><p> cDrug Discovery Unit, Department of Pharmaceutical Sciences, Faculty of Pharmacy, </p><p>University of Jordan, Amman, Jordan</p><p>*Corresponding Author,</p><p>Telephone: 00962 6 5355000 ext. 23305.</p><p>Fax: 00962 6 5339649.</p><p>Email: [email protected]</p><p>Figure SM1: Two views of three-dimensional plot showing three main principal com- ponents calculated for Chk1 testing set (based on 12 physicochemical descriptors, see text). Red triangles (▲) represent active member compounds (IC50 ≤ 10) while blue spheres (●) represent inactive compounds (IC50 > 500) as enlisted in CHEMBL data- base. </p><p>Figure SM2: Two views of three-dimensional plot showing three main principal com- ponents calculated for BACE1 testing set (based on 12 physicochemical descriptors, see text). Red triangles (▲) represent active member compounds (IC50 ≤ 10) while blue spheres (●) represent inactive compounds (IC50 > 500) as enlisted in CHEMBL data- base. Section SM-1: ROC analysis</p><p>ROC curve is plotted by considering the highest score of an active molecule as the </p><p> first threshold then counting the number of inactive compounds within this cut-off </p><p> value, and both the corresponding sensitivity (Se) and specificity (Sp) are calculated </p><p> using equation 1 and equation 2, respectively. This process is repeated using the ac-</p><p> tive molecule possessing the second highest score and so on, until the scores of all ac-</p><p> tive compounds are considered as selection cut-off values [41].</p><p>Number of Selected Actives TP Se   ………………….. (1) Total Number of Actives TP  FN</p><p>….…….……….. (2) Number of Discarded Inactives TN Sp   Total Number of Inactives TN  FP where, TP (true positive) is the number of active compounds that are captured by the </p><p> pharmacophore under concern, FN (false negative) is the number of active com-</p><p> pounds discarded from the hits list, TN (true negative) is the number of discarded de-</p><p> coys , while FP (false positive) is the number of captured decoys .</p><p>The ROC curve for ideal distributions, where active compounds are completely sepa-</p><p> rate and distinct from the inactives (i.e., no overlap between actives and decoys), the </p><p> curve arise vertically to the upper-left corner (Se = Sp = 1) and then joins the up-</p><p> per-right corner horizontally. Hence, the more a ROC curve bends towards the upper </p><p> left corner of the diagram, the more distinct the signal appears [41].</p><p>In practice, the ROC curve for a set of actives and decoys with randomly distributed </p><p> scores tends towards the Se = 1-Sp line asymptotically with increasing number of ac-</p><p> tives and decoys.33 The success of particular virtual screening workflow depending </p><p> on ROC analysis evaluation can be provided as follow: 1) Area under the ROC curve (AUC): which range from 0.5 to 1, where 1 indicates an optimal value and 0.5 random distribution. Whereas an AUC value lower than 0.5 represents the unfavourable case of a virtual screening method that has a higher prob- ability to assign the best scores to decoys than to actives [41].</p><p>2) Overall specificity (SPC): that describes the percentage of discarded inactive by the particular virtual screening workflow. Inactive test compounds are assigned a binary score value of zero (compound not captured) or one (compound captured) [41-43].</p><p>3) Overall true positive rate (TPR or overall sensitivity): describes the fraction per- centage of captured actives from the total number of actives. Active test compounds are assigned a binary score value of zero (compound not captured) or one (compound captured) [41-43].</p>