Computational Drug Discovery and Design

3. Targeted protein’s preprocessing and refinement can be per-
   form by other tools like Schrodinger Protein preparation wiz-
   ard (https://www.schrodinger.com/protein-preparation-
   wizard) and 3D refine web server (http://sysbio.rnet.mis
   souri.edu/3Drefine/)[89–91].


4. The physical–chemical and pharmaceutical properties [92] can
   also be predicted for de novo designed ligands using some tools
   like QikProp (https://www.schrodinger.com/qikprop)[93],
   TOPKAT (http://accelrys.com/products/collaborative-sci
   ence/biovia-discovery-studio/qsar-admet-and-predictive-toxi
   cology.html)[94] SwissADME (https://www.swissadme.ch)
   [95] and admetSAR (http://lmmd.ecust.edu.cn:8000/)
   [96]. These tools are effective and possess wide range of prop-
   erties to predict more insights on the ligands.


5. Prior to docking study, the newly designed compounds could
   be prepared using LigPrep utility of Schrodinger’s package
   [89, 97], which produces all feasible tautomeric, stereochemi-
   cal, and ionization variants of the participation molecules fol-
   lowed by energy minimization to achieve structures with
   optimized geometry.


6. The synthetic accessibility of a compound can be predicted
   with the help of several computational approaches such as
   myPresto—Medicinally Yielding PRotein Engineering Simula-
   TOr program suite (http://presto.protein.osaka-u.ac.jp/
   myPresto4/) and SYLVIA (https://www.mn-am.com/
   products/sylvia)[98].


7. Prediction of binding free energy of the newly designed against
   protein target through MM/GBSA [Molecular Mechanics
   Generalized Born Surface Area continuum solvation] would
   give higher clarity than docking scores in silico or in vitro
   processing [99]


8. Characterization of newly designed ligands through Density
   functional theory calculation on chemical properties such as
   molecular electrostatic potential (MESP), highest occupied
   molecular orbitals (HOMOs) and lowest unoccupied molecu-
   lar orbitals (LUMOs), and aqueous solvation energy would
   provide key mechanistic insights on ligands which will we
   very useful in screening the newly designed ligands before
   further processing [100].

Acknowledgment

SKS thanks Department of Biotechnology (DBT), New Delhi for

providing financial support. VS and UP gratefully acknowledge

DST (New Delhi) for INSPIRE Senior Research Fellowship

De Novo Design of Ligands 81