Movie S4 3-D reconstruction of Ebola virus spike. This movie shows the three-dimensional structure of the of the Ebola virus GP spike. The structure rotates showing views from different angles, and indicates the location of the docked 3CSY.pdb [42] structure with the GP1 and GP2 domains and KZ52 antibody (purple). (MOV) 3D QSAR Pharmacophore Modeling, in Silico Screening, and Density Functional Theory (DFT) Approaches for Identification of Human Chymase Inhibitors Human chymase is a very important target for the treatment of cardiovascular diseases. Using a series of theoretical methods like pharmacophore modeling, database screening, molecular docking and Density Functional Theory (DFT) calculations, an investigation for identification of novel chymase inhibitors, and to specify the key factors crucial for the binding and interaction between chymase and inhibitors is performed. A highly correlating (r = 0.942) pharmacophore model (Hypo1) with two hydrogen bond acceptors, and three hydrophobic aromatic features is generated. After successfully validating “Hypo1”, it is further applied in database screening. Hit compounds are subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with key active site amino acids are identified as potent chymase hits. Moreover, DFT study is performed which confirms very clear trends between electronic properties and inhibitory activity (IC(50)) data thus successfully validating “Hypo1” by DFT method. Therefore, this research exertion can be helpful in the development of new potent hits for chymase. In addition, the combinational use of docking, orbital energies and molecular electrostatic potential analysis is also demonstrated as a good endeavor to gain an insight into the interaction between chymase and inhibitors. Raised blood pressure, especially systolic pressure (hypertension), is one of the striking factors inducing various diseases like heart failure, stroke, myocardial infarction and arterial aneurysm, and is a leading cause of chronic kidney failure [1] . A treatment of hypertension is to decrease the circulating volume and/or to slack the blood vessels [2] . Angiotensin II has important roles not only in the regulation of blood pressure but also in the development of vascular wall remodeling [3] . Conversion of angiotensin I (Ang I) to angiotensin II (Ang II) is catalyzed by well-known angiotensin-converting enzyme (ACE), which is a metallo-proteinase with dipeptidyl-carboxypeptidase activity. However, chymase (EC 3.4.21.39) which is a chymotrypsin-like enzyme expressed in the secretory granule of mast cells, also catalyzes the production of angiotensin II in vascular tissues even when ACE is blocked ( Figure 1 ).