Quantum mechanical-based strategies in drug discovery: Finding the pace to new challenges in drug design

Current Opinion in Structural Biology, Год журнала: 2024, Номер 87, С. 102870 - 102870

Опубликована: Июнь 24, 2024

The expansion of the chemical space to tangible libraries containing billions synthesizable molecules opens exciting opportunities for drug discovery, but also challenges power computer-aided design prioritize best candidates. This directly hits quantum mechanics (QM) methods, which provide chemically accurate properties, subject small-sized systems. Preserving accuracy while optimizing computational cost is at heart many efforts develop high-quality, efficient QM-based strategies, reflected in refined algorithms and approaches. QM-tailored physics-based force fields coupling QM with machine learning, conjunction computing performance supercomputing resources, will enhance ability use these methods discovery. challenge formidable, we undoubtedly see impressive advances that define a new era.

Язык: Английский

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In silico screening of LRRK2 WDR domain inhibitors using deep docking and free energy simulations

Chemical Science, Год журнала: 2024, Номер 15(23), С. 8800 - 8812

Опубликована: Янв. 1, 2024

In this work, we combined Deep Docking and free energy MD simulations for the in silico screening experimental validation potential inhibitors of leucine rich repeat kinase 2 (LRRK2) targeting WD40 (WDR) domain.

Язык: Английский

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Multi-scale computational modeling to identify novel chemical scaffolds as trehalose-6-phosphate phosphatase inhibitors to combat Burkholderia pseudomallei

In Silico Pharmacology, Год журнала: 2025, Номер 13(1)

Опубликована: Фев. 1, 2025

Язык: Английский

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Dynamic Profiling of β-Coronavirus 3CL M^pro Protease Ligand-Binding Sites

Journal of Chemical Information and Modeling, Год журнала: 2021, Номер 61(6), С. 3058 - 3073

Опубликована: Июнь 14, 2021

β-coronavirus (CoVs) alone has been responsible for three major global outbreaks in the 21st century. The current crisis led to an urgent requirement develop therapeutics. Even though a number of vaccines are available, alternative strategies targeting essential viral components required as backup against emergence lethal variants. One such target is main protease (Mpro) that plays indispensable role replication. availability over 270 Mpro X-ray structures complex with inhibitors provides unique insights into ligand-protein interactions. Herein, we provide comprehensive comparison all nonredundant ligand-binding sites available SARS-CoV2, SARS-CoV, and MERS-CoV Mpro. Extensive adaptive sampling used investigate structural conservation using Markov state models (MSMs) compare conformational dynamics employing convolutional variational auto-encoder-based deep learning. Our results indicate not dynamically conserved despite high sequence across β-CoV homologs. This highlights complexity enzymes single pan inhibitor.

Язык: Английский

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The Repurposed ACE2 Inhibitors: SARS-CoV-2 Entry Blockers of Covid-19

Topics in Current Chemistry, Год журнала: 2021, Номер 379(6)

Опубликована: Окт. 8, 2021

The highly infectious disease COVID-19 is induced by SARS-coronavirus 2 (SARS-CoV-2), which has spread rapidly around the globe and was announced as a pandemic World Health Organization (WHO) in March 2020. SARS-CoV-2 binds to host cell's angiotensin converting enzyme (ACE2) receptor through viral surface spike glycoprotein (S-protein). ACE2 expressed oral mucosa can therefore constitute an essential route for entry of into hosts tongue lung epithelial cells. At present, no effective treatments are yet place. Blocking virus inhibiting more advantageous than subsequent stages life cycle. Based on current published evidence, we have summarized different silico based studies repurposing anti-viral drugs target ACE2, S-Protein: S-RBD: ACE2. This review will be useful researchers looking effectively recognize deal with SARS-CoV-2, development repurposed inhibitors against COVID-19.

Язык: Английский

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