Complete reconstruction of dasatinib unbinding pathway from c-Src kinase by supervised molecular dynamics simulation method; assessing efficiency and trustworthiness of the method.
J Biomol Struct Dyn
; 40(23): 12535-12545, 2022.
Article
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| MEDLINE
| ID: mdl-34472425
ABSTRACT
Over the past years, rational drug design has gained lots of attention since employing it gave the world targeted therapy and more effective treatment solutions. Structure-based drug design (SBDD) is an excellent tool in rational drug design that takes advantage of accurate methods such as unbiased molecular dynamics (UMD) simulation for designing and optimizing molecular entities by understanding the binding and unbinding pathways of the binders. Supervised molecular dynamics (SuMD) simulation is a branch of UMD in which long-duration simulations are turned into short simulations, called replica, and a specific parameter is monitored throughout the simulation. In this work, we utilized this strategy to reconstruct the unbinding pathway of the anticancer drug dasatinib from its target protein, the c-Src kinase. Several unbinding events with valuable details were achieved. Then, to assess the efficiency and trustworthiness of the SuMD method, the unbinding pathway was also reconstructed by conventional UMD simulation, which uncovered some of the limitations of this method, such as limited sampling of the active site and finding the metastable states in the unbinding pathway. Furthermore, in times like these, when the world is desperate to find treatments for the Covid-19 disease, we think these methods are of exceptional value.Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación de Dinámica Molecular
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COVID-19
Límite:
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2022
Tipo del documento:
Article
País de afiliación:
Irán
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM