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Computer-based techniques for lead identification and optimization I: Basics

Annalisa Maruca
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  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Francesca Alessandra Ambrosio
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Antonio Lupia
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Isabella Romeo
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Roberta Rocca
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
  • Department of Experimental and Clinical Medicine, Magna Graecia University and Traslational Medicinal Oncology Unit, Salvatore Venuta University Campus, Catanzaro, Italy
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/ Federica Moraca
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
  • Department of Chemical Sciences, University of Napoli Federico II, Via Cinthia 4, I-80126 Napoli, Italy
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/ Carmine Talarico
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Donatella Bagetta
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Raffaella Catalano
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Giosuè Costa
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Anna Artese
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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/ Stefano Alcaro
  • Department of Health Sciences, University “Magna Græcia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
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Published Online: 2019-01-11 | DOI: https://doi.org/10.1515/psr-2018-0113


This chapter focuses on computational techniques for identifying and optimizing lead molecules, with a special emphasis on natural compounds. A number of case studies have been specifically discussed, such as the case of the naphthyridine scaffold, discovered through a structure-based virtual screening (SBVS) and proposed as the starting point for further lead optimization process, to enhance its telomeric RNA selectivity. Another example is the case of Liphagal, a tetracyclic meroterpenoid extracted from Aka coralliphaga, known as PI3Kα inhibitor, provide an evidence for the design of new active congeners against PI3Kα using molecular dynamics (MD) simulations. These are only two of the numerous examples of the computational techniques’ powerful in drug design and drug discovery fields. Finally, the design of drugs that can simultaneously interact with multiple targets as a promising approach for treating complicated diseases has been reported. An example of polypharmacological agents are the compounds extracted from mushrooms identified by means of molecular docking experiments. This chapter may be a useful manual of molecular modeling techniques used in the lead-optimization and lead identification processes.

Keywords: drug discovery; drug-like properties; virtual screening; pharmacophore models; molecular recognition; molecular dynamics


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Published Online: 2019-01-11

Citation Information: Physical Sciences Reviews, 20180113, ISSN (Online) 2365-659X, DOI: https://doi.org/10.1515/psr-2018-0113.

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