## 3 QSAR Today
### Descriptors Calculation: Calculate Molecular Descriptors  
The biological, chemical, and physical properties of chemical compounds are determined by their chemical structure. Molecular description addresses another significant topic: the computer-based representation of molecular structures. Descriptors should be computed from the chemical structure of compounds. If the compounds are well described, QSAR models can accurately predict the activities of novel compounds before their synthesis.  
The \"Handbook of Molecular Descriptors\", first published in 2000, provides a comprehensive overview of this topic [80]. New descriptors are introduced every year, aiming to identify the most suitable descriptor for specific chemical, biological, or physical properties. Various software tools are available for calculating molecular descriptors, including ACD/Labs (logP, logS, logD, pKa) [81], DRAGON and E-DRAGON (constitutional, topological, 2D-autocorrelations, geometrical, WHIM, GETAWAY, RDF, functional groups, etc.) [82; 83; 84], CDK (topological, geometrical, electronic, and constitutional) [85], CODESSA PRO (constitutional, topological, geometrical, charge-related, semi-empirical, thermodynamical) [86], MOE (topological, physical properties, structural keys, etc.) [87; 88], MOLD2 (1D and 2D descriptors) [89; 90], PowerMV (Constitutional, atom pairs, fingerprints, BCUT) [91], and PreADMET (constitutional, topological, geometrical, and physicochemical descriptors) [92]. While some of these tools are commercial, others are available as freeware.  
Descriptor types can be classified based on dimensionality, referring to the number of geometric dimensions considered. Thus, 0D and 1D descriptors provide basic molecular information like molecular weight and number of constituent elements. Two-dimensional descriptors include topological indices computed from structural formulas, using graph theory [93]. Common examples are the connectivity index [94; 95; 96], Wiener's index [97], Zagreb indices [98], Balaban's J Index [99] and Kier shape indices [100]. Three-dimensional descriptors rely on three-dimensional atomic coordinates. They can be alignment-dependent, including Comparative Molecular Field Analysis (CoMFA) [101], Comparative Molecular Similarity Indices Analysis (CoMSIA) [102], Comparative Binding Energy Analysis (CoM-BINE) [103], Comparative Residue Interaction Analysis (CoRIA) [104], and Hint Interaction Field Analysis (HIFA) [105], and alignment-independent including Comparative Molecular Moment Analysis (CoMMA) [106], Comparative Spectral Analysis (CoSA) [107], and Hologram-QSAR (HQSAR or Holo-QSAR) [108].  
Descriptors can be categorized based on the molecular properties they represent, including constitutional, topological, geometrical, electronic, and thermodynamic characteristics [109; 110]. Constitutional descriptors provide information about the molecular composition without considering atom connectivity. Examples include molecular weight, atom and bond counts, and elemental composition. Topological descriptors describe how atoms are connected within a molecule using molecular graph representations. Geometrical descriptors use the 3D coordinates of atoms to capture molecular size, shape, and atom distribution, including steric parameters such as molecular volume and surface area. Electronic descriptors characterize the electronic structure of a molecule, including properties like dipole and quadrupole moments, polarizabilities, atomic charges, and the energies of HOMO and LUMO orbitals. Thermodynamic descriptors reflect chemical behaviors related to energy, such as heat of formation and molar refractivity. For further reading, see references [109; 110; 111; 112; 113; 114].