Module 6 Computer Aided Drug design & Preformulation studies Flashcards
The inventive process of finding new medications based on the knowledge of a biological target.
Drug Design
It involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it.
Drug Design
LIFE CYCLE OF DRUG DESIGN:
Traditional Life Cycle
Ist step: Synthetic Or natural product
2nd step: Preclinical trials
3rd step: Clinical trials
Drug
LIFE CYCLE OF DRUG DESIGN:
Modern Drug Design
Ist step: Target Selection
2nd step: Lead Identification
3rd step: Lead Optimization
Drug
DRUG DESIGNING:
Selected/ design molecules should be:
•Organic small molecule
•Complementary in shape to the target
•Oppositely charge to the biomolecular target
DRUG DESIGNING…
This molecule will:
•Interact with the target
•Bind to the target
•Activates or inhibit the function of a biomolecule such as protein
DRUG DESIGNING:
Drug designing frequently but not necessarily relies on computer modelling techniques.
This type of modelling is sometimes referred to as computer aided design.
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Drug discovery approaches:
In Vitro
1. Biochemical estimation
2. Toxicity asay
3. Assays on drug susceptibility
4. Effects on biofilm
In Vivo
1. Bioavailability
2. Toxicity
3. ADME
4. Pharmacodynamics
5. Pharmacokinetics
In Silico
1. Computer-aided drug discovery
2. Molecular docking
3. Molecular modeling
4. Virtual screening
5. Quantitative structure–activity relationship (QSAR)
The term ‘____’ is a modern word usually used to mean experimentation performed by computer and is related to the more commonly known biological terms in vivo and in vitro.
Process, identification of the suitable drug target is the first and foremost task.
These targets are biomolecules which mainly include DNA, RNA and proteins (such as receptors, transporters, enzymes and ion channels).
in silico
uses computational approaches to discover, develop, and analyze drugs and similar biologically active molecules.
COMPUTER-AIDED DRUG DESIGN (CADD)
Computer-aided drug discovery
Characteristic features of CADD:
Virtual screening
Energy calculations
ADME models
Drug interactions
2 CATEGORIES OF “IN SILICO” BASED DRUG DESIGN:
Ligand-based drug design
Structure-based drug design
The basic objective of these methods is to predict the nature and strength of binding of given molecule to a target.
Ligand-based drug design
Involves the analysis of ligands known to interact with a target of interest.
These methods use a set of reference structures collected from compounds known to interact with the target of interest and analyze their 2D or 3D structures.
This is an indirect approach where analysis is totally dependent on information of other molecules that attach to the target compound of interest.
Ligand-based drug design
These other molecules may be used to develop a pharmacophore model that delineates the minimum needed structural characteristics a molecule must hold in order to bind to the target successfully.
Precisely a model of the biological target may be constructed on the facts of what binds to it.
This knowledge could be further implemented to design new molecular entities that interact with the target.
Ligand-based drug design
This is relatively a direct approach which is based on the knowledge of the three-dimensional structure of the biological target obtained through methods such as X-ray, crystallography, or NMR spectroscopy which are mainly the starting point for gathering information in the field of drug discovery and development
Structure-based drug design
In case of unavailability of the target structure, prediction using a related protein’s experimental structure is carried out by generating a homology model of the target.
Based on this data drug that seems to be exhibiting high affinity for the target is selected and further computational trials are employed to suggest new drug candidates.
Structure-based drug design
It works with the basic understanding of structure prediction of intermolecular complex formed between drug and its target molecule.
It gives other important information like extent and specificity of interaction, binding and transformation energies.
MOLECULAR DOCKING
is a pharmacologically important tool in the field of drug designing and computational biology
Docking
A method of comparing and analyzing molecular structures, 3D structure-based properties, and their interactions.
Primary applicability of this technique generates data on receptor ligand interaction, protein-protein interactions, 3D structure prediction, and based on this predicting biological function of related compounds.
MOLECULAR MODELING
The key methodology applied in drug discovery studies for the identification of new hits.
Receptor structure based as well as non receptor based methods could be employed to design ligand
VIRTUAL SCREENING
establishes a relation between predictor and response variables by applying graphical and mathematical models.
For prediction and evaluation of compound binding modes mathematical relationships between structural attributes and target properties of a set of chemicals are studied
Quantitative structured activity relationship (QSAR)
is a group of studies that focus on the physicochemical properties of a new drug candidate that could affect the drug performance and the development of a dosage form.
This could provide important information for formulation design or support the need for molecular modification.
Preformulation studies
The overall objective of pre formulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms which can be mass-produced
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