Yada: a novel tool for molecular docking calculations

The growing number of studies on G protein-coupled receptors (GPCRs) family are a source of noticeable improvement in our understanding of the functioning of these proteins. GPCRs are responsible for a vast part of signaling in vertebrates and, as such, invariably remain in the spotlight of medicinal chemistry. A deeper insight into the underlying mechanisms of interesting phenomena observed in GPCRs, such as biased signaling or allosteric modulation, can be gained with experimental and computational studies. The latter play an important role in this process, since they allow for observations on scales inaccessible for most other methods. One of the key steps in such studies is proper computational reconstruction of actual ligand-receptor or protein-protein interactions, a process called molecular docking. A number of improvements and innovative applications of this method were documented recently. In this review, we focus particularly on innovations in docking to GPCRs.

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“…One of such recently released algorithms is Yada [ 55 ]. It is a freely available tool reported in September 2016.…”

Section: An Overview Of Docking Of Small Molecules To Gpcrsmentioning

confidence: 99%

Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors

et al. 2017

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“…The conservation string ranges from 9 for very conserved residues to 1 for no conserved amino acids, as described in ref. [ 47 ].…”

Section: Methodsmentioning

confidence: 99%

Hydroxylated Fatty Acids: The Role of the Sphingomyelin Synthase and the Origin of Selectivity

et al. 2021

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Sphingolipids are a class of lipids acting as key modulators of many physiological and pathophysiological processes. Hydroxylation patterns have a major influence on the biophysical properties of sphingolipids. In this work, we have studied the mechanism of action of hydroxylated lipids in sphingomyelin synthase (SMS). The structures of the two human isoforms, SMS1 and SMS2, have been generated through neural network supported homology. Furthermore, we have elucidated the reaction mechanism that allows SMS to recover the choline head from a phosphocholine (PC) and transfer it to ceramide, and we have clarified the role of the hydroxyl group in the interaction with the enzyme. Finally, the effect of partial inhibition of SMS on the levels of PC and sphingomyelin was calculated for different rate constants solving ordinary differential equation systems.

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“…In docking, the water molecules associated to the binding pockets can be determinant in the development of drug candidates that may establish distinct types of interactions with the protein target [44]. Several docking tools take into account the intervention of water molecules in protein-ligand interaction, such as Yet Another Docking Approach (YADA) [566], which considers the explicitly structural water molecules at the binding site and improves the prediction scores by up to 24%. Another docking software, Molegro Virtual Docker (MVD) [567], incorporates water molecules in protein-ligand complexes and considers that water molecules exhibit the same flexibility of the ligand.…”

Section: Relevant Features In Gpcr-ligand Interactionsmentioning

confidence: 99%

In Silico Studies Targeting G-protein Coupled Receptors for Drug Research Against Parkinson’s Disease

Lemos

Melo

Preto

et al. 2018

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Parkinson's Disease (PD) is a long-term neurodegenerative brain disorder that mainly affects the motor system. The causes are still unknown, and even though currently there is no cure, several therapeutic options are available to manage its symptoms. The development of novel antiparkinsonian agents and an understanding of their proper and optimal use are, indeed, highly demanding. For the last decades, L-3,4-DihydrOxyPhenylAlanine or levodopa (L-DOPA) has been the gold-standard therapy for the symptomatic treatment of motor dysfunctions associated to PD. However, the development of dyskinesias and motor fluctuations (wearing-off and on-off phenomena) associated with long-term L-DOPA replacement therapy have limited its antiparkinsonian efficacy. The investigation for non-dopaminergic therapies has been largely explored as an attempt to counteract the motor side effects associated with dopamine replacement therapy. Being one of the largest cell membrane protein families, G-Protein-Coupled Receptors (GPCRs) have become a relevant target for drug discovery focused on a wide range of therapeutic areas, including Central Nervous System (CNS) diseases. The modulation of specific GPCRs potentially implicated in PD, excluding dopamine receptors, may provide promising non-dopaminergic therapeutic alternatives for symptomatic treatment of PD. In this review, we focused on the impact of specific GPCR subclasses, including dopamine receptors, adenosine receptors, muscarinic acetylcholine receptors, metabotropic glutamate receptors, and 5-hydroxytryptamine receptors, on the pathophysiology of PD and the importance of structure- and ligand-based in silico approaches for the development of small molecules to target these receptors.

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Yada: a novel tool for molecular docking calculations

Cited by 15 publications

References 19 publications

Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors

Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors

Hydroxylated Fatty Acids: The Role of the Sphingomyelin Synthase and the Origin of Selectivity

In Silico Studies Targeting G-protein Coupled Receptors for Drug Research Against Parkinson’s Disease

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