Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation From HIV-1 Protease DOI Open Access

Emily Vig,

Jianan Sun, Chia‐en A. Chang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 16, 2024

ABSTRACT Investigation of protein-drug recognition is key in understanding drug selectivity and binding affinity. In combination, binding/unbinding free energy landscape intermolecular interactions can be used to understand the mechanisms. This information vital for development drugs with improved efficacy explanation mutation effects. study investigated dissociation processes ritonavir unbinding from HIV protease (HIVp). Analyzing trajectories modeled by accelerated molecular dynamics (MD) simulations, three distinct pathways, Pathways A, B, C, were characterized. Using reduced dimensionality strategy principal component analysis, we carried out short classical MD runs explicit water sample local fluctuation during applied milestoning theory construct landscape. We found that each pathway showed similar values energy, albeit Pathway A accounts over 50 percent trajectories. Interesting, residue-residue correlation network analysis a broad outside flap region governs protein motions which includes residues reported However, other two pathways limited networks where no mutated involved, explaining favorability A. Guided profile, how why an barrier minimum demonstrated hydrogen bonding governed movement regions, directly impacting calculated energy. Our provided new estimate ligand importance transient ligand-protein unbinding.

Язык: Английский

Ritonavir enhances the efficacy of amprenavir: A promising combination therapy by targeting Leishmania DNA topoisomerase I for treatment of visceral leishmaniasis DOI

Priyanka H. Mazire,

Snehal Shingade, Amit Roy

и другие.

Experimental Parasitology, Год журнала: 2025, Номер 269, С. 108898 - 108898

Опубликована: Янв. 10, 2025

Язык: Английский

Процитировано

0
Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation from HIV-1 Protease DOI

Emily Vig,

Jianan Sun, Chia‐en A. Chang

и другие.

Biochemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 9, 2025

Investigation of protein–drug recognition is key to understanding drug selectivity and binding affinity. In combination, the binding/unbinding free energy landscape intermolecular interactions can be used understand mechanisms. This information vital for development drugs with improved efficacy explanation mutation effects. study investigated dissociation processes ritonavir unbinding from HIV protease (HIVp). Analyzing trajectories modeled by accelerated molecular dynamics (MD) simulations, three distinct pathways, pathways A–C, were characterized. Using a reduced dimensionality strategy principal component analysis, we carried out short classical MD runs explicit water sample local fluctuation during applied milestoning theory construct an landscape. We found that each pathway showed similar values energy, albeit A accounts over 50% trajectories. Interestingly, residue–residue correlation network analysis in A, broad outside flap region governs protein motions unbinding, which includes residues reported However, other two limited networks where no mutated involved, explaining favorability A. Guided profile, barrier minimum, demonstrating hydrogen bonding governed movement regions, directly impacting calculated energy. Our provided new estimate ligand demonstrated importance transient ligand–protein unbinding.

Язык: Английский

Процитировано

0
Pharmacovigilance of Drug–Drug Interactions with Nirmatrelvir/Ritonavir DOI Creative Commons
Victoria Hendrick,

Erast Pohorylo,

Lubna Merchant

и другие.

Infectious Diseases and Therapy, Год журнала: 2024, Номер unknown

Опубликована: Окт. 26, 2024

Язык: Английский

Процитировано

2
COVID-19 and Cancer Care: A Review and Practical Guide to Caring for Cancer Patients in the Era of COVID-19 DOI Creative Commons

Simon Claveau,

Farhan Mahmood, Baraa Amir

и другие.

Current Oncology, Год журнала: 2024, Номер 31(9), С. 5330 - 5343

Опубликована: Сен. 10, 2024

COVID-19, a novel infectious disease caused by the emergence of SARS-CoV-2 virus in 2020, has had profound impact on healthcare, both at individual and population level. The level was felt most acutely during emergency phase pandemic, with hospital capacity issues leading to widespread disruptions delays delivery healthcare services such as screening programs elective surgeries. While hospitals are no longer being overwhelmed COVID-19 patients, vulnerable patient populations cancer patients continues be ongoing consequence. Cancer remain high risk hospitalization, ICU admission, death due even era vaccination. Infection prevention mitigation strategies air quality control, masking, testing, vaccination, treatment should therefore integrated into usual care counseling moving forward avoid preventable morbidity mortality from this infection ensure safety cohort they navigate their diagnosis COVID-19.

Язык: Английский

Процитировано

0
Pathway Specific Unbinding Free Energy Profiles of Ritonavir Dissociation From HIV-1 Protease DOI Open Access

Emily Vig,

Jianan Sun, Chia‐en A. Chang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 16, 2024

ABSTRACT Investigation of protein-drug recognition is key in understanding drug selectivity and binding affinity. In combination, binding/unbinding free energy landscape intermolecular interactions can be used to understand the mechanisms. This information vital for development drugs with improved efficacy explanation mutation effects. study investigated dissociation processes ritonavir unbinding from HIV protease (HIVp). Analyzing trajectories modeled by accelerated molecular dynamics (MD) simulations, three distinct pathways, Pathways A, B, C, were characterized. Using reduced dimensionality strategy principal component analysis, we carried out short classical MD runs explicit water sample local fluctuation during applied milestoning theory construct landscape. We found that each pathway showed similar values energy, albeit Pathway A accounts over 50 percent trajectories. Interesting, residue-residue correlation network analysis a broad outside flap region governs protein motions which includes residues reported However, other two pathways limited networks where no mutated involved, explaining favorability A. Guided profile, how why an barrier minimum demonstrated hydrogen bonding governed movement regions, directly impacting calculated energy. Our provided new estimate ligand importance transient ligand-protein unbinding.

Язык: Английский

Процитировано

0