Молекулярное моделирование – современный подход к разработке лекарств. Принципы молекулярного моделирования. Разработка лекарств. Применение молекулярного моделирования.
Molecular modeling principles
Drug discovery
Molecular modeling applications
Molecular modeling in drug discovery
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Molecular modeling principles
Optimization
The determination of a low-energy conformation for a given force field can be the final goal of the computation.
Minimization of Josacine structure
Molecule
Molecule – a central object of molecular modeling.
Drug discovery
Drug discovery includes four stages:
- target identification and validation
- lead identification
- lead optimization
- biological testing
Target selection
Target selection is based on information about human diseases and the biological processes that lead to a particular disease.
Anaplastic lymphoma kinase – enzyme encoded by the ALK gene that can be oncogenic
Identification of a suitable lead molecule (potential drug)
It is achieved through screening of available chemical compound libraries and natural products.
Crizotinib – anti-cancer drug, ALK inhibitor
Optimization of a lead molecule
The purpose is to acquire molecules with demanded properties.
Structure of Aspirin Acetylated Cyclooxygenase-1 in Complex with Diclofenac
Testing of lead compounds
This stage includes investigating of different characteristics, studies in animals, clinical tests.
HIV-1 proteinase complexed with Saquinavir
Molecular modeling applications
Generation of chemical structure
Chlorpropamide – anti-diabetic drug
Visualization of molecular structure
Vildagliptin – anti-diabetic drug
Determination of molecular properties
- Monte Carlo method
- Molecular dynamics
Josacine structure
Molecular modeling in drug discovery
Discovery of cannabinoid analogues for therapeutic use
Structural based drug design of HIV-1 Protease
HIV-1 proteinase complexed with Saquinavir
Molecular modeling approaches to anti-angiogenic cancer therapeutics
Structure of the human anaplastic lymphoma kinase in complex with Crizotinib