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    Drug Design: Prepared By: DR Mazlin Mohideen B.Pharm Tech, FPHS, Unikl-Rcmp

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    Yana Qis
    This document discusses drug design and computer-aided drug design (CADD). It describes two main approaches for drug design using CADD: structure-based drug design which uses the target protein structure, and ligand-based drug design which uses known active ligands. Key techniques discussed include virtual screening, molecular docking, and structure-activity relationships. CADD can reduce drug discovery costs and time by eliminating compounds with undesirable properties through in silico screening before biological testing.

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    Drug Design: Prepared By: DR Mazlin Mohideen B.Pharm Tech, FPHS, Unikl-Rcmp

    Uploaded by

    Yana Qis
    72 views22 pages
    This document discusses drug design and computer-aided drug design (CADD). It describes two main approaches for drug design using CADD: structure-based drug design which uses the target protein structure, and ligand-based drug design which uses known active ligands. Key techniques discussed include virtual screening, molecular docking, and structure-activity relationships. CADD can reduce drug discovery costs and time by eliminating compounds with undesirable properties through in silico screening before biological testing.

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    This document discusses drug design and computer-aided drug design (CADD). It describes two main approaches for drug design using CADD: structure-based drug design which uses the target protein structure, and ligand-based drug design which uses known active ligands. Key techniques discussed include virtual screening, molecular docking, and structure-activity relationships. CADD can reduce drug discovery costs and time by eliminating compounds with undesirable properties through in silico screening before biological testing.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    72 views22 pages

    Drug Design: Prepared By: DR Mazlin Mohideen B.Pharm Tech, FPHS, Unikl-Rcmp

    Uploaded by

    Yana Qis
    This document discusses drug design and computer-aided drug design (CADD). It describes two main approaches for drug design using CADD: structure-based drug design which uses the target protein structure, and ligand-based drug design which uses known active ligands. Key techniques discussed include virtual screening, molecular docking, and structure-activity relationships. CADD can reduce drug discovery costs and time by eliminating compounds with undesirable properties through in silico screening before biological testing.

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    CHAPTER 3:

    DRUG DESIGN

    PREPARED BY: DR MAZLIN MOHIDEEN


    B.PHARM TECH, FPHS, UNIKL-RCMP
    [email protected]
    H/P: 013-2656432
    DRUG DESIGN
    ❑ Drug design, referred to as rational drug design or more simply rational
    design, is the inventive process of finding new medications based on the
    knowledge of a biological target.

    A. Optimizing target interactions

    B. Optimizing access to the target


    Specific Terms:

    Rational design - which invites A biological target is anything


    the strategy of creating new within a living organism to which
    molecules with a certain some other entity (like an
    functionality, based upon the endogenous ligand or a drug) is
    ability to predict how the directed and/or binds, resulting in a
    molecule's structure will affect change in its behaviour or function.
    its behaviour through physical Examples: proteins and nucleic
    models. acid.
    ❑ In basic sense, drug design 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.

    ❑ The phrase "drug design" is referred to ligand design (design of a molecule that
    will bind tightly to its target). Although design techniques for prediction of binding
    affinity are reasonably successful, there are many other properties, such as
    bioavailability, metabolic half-life, side effects, must be optimized before a ligand
    can become a safe and efficacious drug.
    COMPUTER-AIDED DRUG DESIGN (CADD)
    ❑ Computational approaches in drug design,
    discovery and development process gaining very
    rapid exploration, implementation and admiration.

    ❑ Introducing a new drug in a market is a very


    complex, risky and costly process in terms of time,
    money and manpower.

    ❑ Generally it is found that drug discovery and


    development process takes around 10-14 years
    and more than 1 billion dollars capital in total.
    ❑ for reducing time, cost and risk borne factors:

    - CADD method is widely used as a new drug


    design approach.

    - by the use of CADD approaches can


    reduced the cost of drug discovery and
    development up to 50%.

    ❑ CADD consist use of any software program


    based process for establishing a standard to
    relate activity to structure.
    Major types of approaches in CADD

    TWO types of approaches for drug


    design through CADD:

    1. Structure based drug design / direct


    approach

    2. Ligand based drug design / indirect


    approach
    1. Structure-Based Drug Design (SBDD)……..

    ❑ In SBDD, structure of the target


    protein is known and interaction or
    bio-affinity for all tested compounds
    calculate after the process of docking;
    to design a new drug molecule, which
    shows better interaction with target
    protein.
    Overview of the process involved in SBDD

    ❑ SBDD runs through multiple cycles before the optimized lead reached into
    clinical trials.
    ▪ The first cycle comprises isolation, purification and structure
    determination of the target protein by one of three key methods: like X-ray
    crystallography, homology modeling or NMR.
    ❑ Using compounds comes through virtual screening of
    different databases are placed into a selected region
    (active site) of the protein.

    ❑ These compounds are scored and ranked on the bases


    of steric, hydrophobic, electrostatic interaction of these
    molecules with the active site of target protein.

    ❑ Top ranked compounds are tested with biochemical


    assays. After several additional cycles like synthesis of
    lead, further optimization of lead through complex
    structure of protein with lead compound, the optimized
    compounds generally show marked increment in the
    target specificity and binding affinity.
    2. Ligand-Based Drug Design (LBDD)……..

    ❑ In LBDD, 3D structure of the target


    protein is not known but the knowledge of
    ligands which binds to the desired target
    site is known.

    ❑ These ligands can be used to develop a


    pharmacophore model or molecule which
    possesses all necessary structural
    features for bind to a target active site.
    ❑ Generally ligand-based techniques are pharmacophore based approach and
    quantitative-structure activity relationships (QSARs).

    ❑ In LBDD it is assumed that compounds which having similarity in their structure


    also having the same biological action and interaction with the target protein.
    Virtual Screening

    ❑ Virtual screening has been worked as a most convenient tool now a day to find
    out the most favourable bioactive compounds with the help of information about
    the protein target or known active ligands.

    ❑ In the recent time virtual screening is known as a mind blowing alternative of


    high-throughput screening (HTs) mainly in terms of cost effectiveness and
    probability of finding most appropriate novel hit through filter the large of libraries
    of compounds.
    ❑ There are generally TWO types of virtual
    screening approaches:
    ▪ structure-based virtual screening (SBVS)
    ▪ ligand-based virtual screening (LBVS)

    ❑ SBVS method rely on the structure of target


    protein active site and LBVS method is
    based on estimation of calculated similarity
    between the known active and compound
    come from databases.
    Molecular Docking

    ❑ is in-silico method - predicts the placement of small molecules or ligands within


    the active site of their target protein (receptor), mainly used to accurate
    estimation of most favorable binding modes and bio-affinities of ligands with their
    receptor, applied to virtual screening for the optimization of the lead compounds.

    ❑ Methodology - which are interconnected to each other like: prediction of binding


    pose, bio affinity and virtual screening. In the molecular docking method the
    basis tools are search algorithm and scoring functions for creating and analyzing
    conformations of the ligand.
    Advantages of CADD

    ❑ Through CADD, can reduce the synthetic and biological testing efforts.

    ❑ It gives the most promising drug candidate by eliminate the compounds with
    undesirable properties (poor efficacy, poor ADMET etc.) through in silico filters.

    ❑ It is a cost-effective, time saving, rapid and automatic process.

    ❑ Through it we can know about the drug-receptor interaction pattern.

    ❑ It gives compounds with high hit rates through searching huge libraries of
    compounds in silico in comparison to traditional high throughput screening.

    ❑ These approaches minimize chances of failures in the final phase.


    CONCLUSION AND FUTURE ASPECTS
    ❑ Computer aided drug design (CADD) is an efficient tool in the area of drug
    discovery and development, through it we can find the most promising drug
    candidate in a very cost-effective way.

    ❑ It always provides a hope for betterment in drug discovery area. In the past
    years through CADD many impressive researches are achieved so it will play a
    very much important role in the near future.

    ❑ With the current achievement’s, there is a promising future of computer aided


    drug design to aid drug discovery of many more curatives in future.
    Thank You

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