Computer-Aided Drug Design Approaches to Study Key Therapeutic Targets in Alzheimer’s Disease

Lemos, Agostinho; Melo, Rita; Moreira, Irina S.; Cordeiro, M. Natália D. S.

doi:10.1007/978-1-4939-7404-7_3

Cited by 3 publications

(1 citation statement)

References 503 publications

(436 reference statements)

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“…They have a role in the coupled binding of extracellular ligands to conformational changes as well as the activation of intracellular G proteins and GPCR kinases. Rhodopsin is activated by light-induced isomerization in the native membranes due to the covalently binding inverse agonist 11-cis retinal to the all-trans-retinal within a very tight binding pocket [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Molecular Docking Study on the Interaction of Rhodopsin-like Receptors with Tetracoordinated Gold(III) Complexes

Kesić

Milenković

Antonijević

et al. 2021

The 1st International Electronic Conference on Biomedicine

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The pharmacologic properties of gold compounds have been known since the end of the 19th century. In the last decade gold complexes have received increased attention due to the variety of their applications. Rhodopsin-like receptors are a family of proteins that belong to the largest group of G-protein-coupled receptors (GPCRs). In this paper the molecular interactions between the active binding sites of rhodopsin-like receptors (RLRs) and synthesized gold(III) complexes ([Au(DPP)Cl2]+, where DPP = 4,7-diphenyl-1,10-phenanthroline) were investigated through molecular docking simulations. The crystal structure of investigated RLRs (PDB ID: 4A4M) was extracted from the RCSB Protein Data Bank in a PDB format. The native bound ligand (11-cis-retinal) was extracted from receptors and a binding pocket analysis was performed. Redocking was performed with gold(III) complexes to generate the same docking pose as found in the cocrystallized form of receptors. The binding energy of gold(III) complexes to RLRs was found to be −35.35 kJ/mol, as opposed to 11-cis-retinal, where it was about −40.5 kJ/mol. The obtained results revealed that gold(III) complexes bind at the same binding pockets to RLRs, as well as native bound ligands, via weak noncovalent interactions. The most prominent interactions are hydrogen bonds, alkyl–π and π–π interactions. The preliminary results suggest that gold(III) complexes showed good binding affinity against RLRs as well as the native bound ligand 11-cis-retinal, as evident from the free binding energy (ΔGbind in kJ/mol).

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Section: Introductionmentioning

confidence: 99%

Molecular Docking Study on the Interaction of Rhodopsin-like Receptors with Tetracoordinated Gold(III) Complexes

Kesić

Milenković

Antonijević

et al. 2021

The 1st International Electronic Conference on Biomedicine

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Arrestin and G Protein Interactions with GPCRs: A Structural Perspective

Barreto¹,

Baptista²,

Bueschbell³

et al. 2022

GPCRs as Therapeutic Targets

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An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

Melo

Lemos

Preto

et al. 2020

CMC

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Paediatric Acquired ImmunoDeficiency Syndrome (AIDS) is a life-threatening and infectious disease in which the Human Immunodeficiency Virus (HIV) is mainly transmitted through Mother-To-Child Transmission (MTCT) during pregnancy, labour and delivery, or breastfeeding. This review provides an overview of the distinct therapeutic alternatives to abolish the systemic viral replication in paediatric HIV-1 infection. Numerous classes of antiretroviral agents have emerged as therapeutic tools for downregulation of different steps in the HIV replication process. These classes encompass Non-Nucleoside Analogue Reverse Transcriptase Inhibitors (NNRTIs), Nucleoside/Nucleotide Analogue Reverse Transcriptase Inhibitors (NRTIs/NtRTIs), INtegrase Inhibitors (INIs), Protease Inhibitors (PIs), and Entry Inhibitors (EIs). Co-administration of certain antiretroviral drugs with Pharmacokinetic Enhancers (PEs) may boost the effectiveness of the primary therapeutic agent. The combination of multiple antiretroviral drug regimens (Highly Active AntiRetroviral Therapy - HAART) is currently the standard therapeutic approach for HIV infection. So far, the use of HAART offers the best opportunity for prolonged and maximal viral suppression, and preservation of the immune system upon HIV infection. Still, the frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, the development of drug resistance and the lack of patient compliance compromise the complete HIV elimination. The development of nanotechnology-based drug delivery systems may enable targeted delivery of antiretroviral agents to inaccessible viral reservoir sites at therapeutic concentrations. In addition, the application of Computer-Aided Drug Design (CADD) approaches has provided valuable tools for the development of anti-HIV drug candidates with favourable pharmacodynamics and pharmacokinetic properties.

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Computer-Aided Drug Design Approaches to Study Key Therapeutic Targets in Alzheimer’s Disease

Cited by 3 publications

References 503 publications

Molecular Docking Study on the Interaction of Rhodopsin-like Receptors with Tetracoordinated Gold(III) Complexes

Molecular Docking Study on the Interaction of Rhodopsin-like Receptors with Tetracoordinated Gold(III) Complexes

Arrestin and G Protein Interactions with GPCRs: A Structural Perspective

An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population

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