DESIGNING DRUGS

VIRTUALLYSAMIHAH BINTI AHMED

ALIAA BINTI MOHAMAD ZIYADINITTIARAJ A/L PERUMAL

BACKGROUNDPharmaceutical companies and medical researchers are constantly trying to find new drugs that will provide better treatments for cancer and other serious illnesses.

Disease fighting drugs – attacks a

disease

Drug is able to stop these

interactions by connecting to

protein

Drug connecting to protein = key

fitting into a lock

Drug companies – create huge of

compounds and use robots to

review samples

Machines – create thousands of

chemicals per day

Robots would drop bits of each

chemical into tiny vials

A hit occurred when substances

and chemical produced desired

reaction

INTRODUCTION Joshua Boger, a former Merck & Company

scientist - decide to try different approach called structure based design.

In 1989, he formed a company called Vertex Pharmaceuticals, which would focus on figuring out what a ‘lock’ looked like so it could fashion the right disease fighting ‘key’.

DETERMINE THE SHAPE OF A ‘LOCK’

Crystallize the proteins and examine the patterns left by the X-rays

Find a custom molecule to fit that particular ‘lock’.

Powerful computers help evaluate the structures and properties of molecules

Identify the most promising candidates

IMPORTANT OF IT Pharmaceutical companies trying to

develop new drugs are very challenged because the drug discovery process is so painstaking and complicated.

Powerful computers for analyzing molecular structure, databases organizing data about specific molecules and compounds, and software for visualizing and modeling molecules all play role in creating new knowledge and making that knowledge available to researches.

WHY ARE COMPUTERS SO IMPORTANT IN DRUG

DISCOVERY?

Use of computational techniques in drug discovery and development process is rapidly gaining in popularity, implementation and appreciation.

Different terms are being applied to this area, including computer-aided drug design (CADD), computational drug design, computer-aided molecular design (CAMD), computer-aided molecular modeling (CAMM), rational drug design, in silico drug design, computer-aided rational drug design.

Both computational and experimental techniques have important roles in drug discovery and development and represent complementary approaches. 

CADD ENTAILS :

Use of computing power to streamline drug discovery and development process

Leverage of chemical and biological information about

ligands and/or targets to identify and optimize new

drugs

Design of in silico filters to eliminate compounds with

undesirable properties (poor activity and/or poor

Absorption, Distribution, Metabolism, Excretion and Toxicity, ADMET) and select

the most promising candidates.

WHAT ROLES ARE PLAYED BY COMPUTERS IN THE DRUG

DISCOVERY PROCESS?

Fast expansion in drug discovery area has been made possible by advances in software and hardware computational power and sophistication, identification of molecular targets, and an increasing database of publicly available target protein structures.

CADDD is being utilized to identify hits (active drug candidates), select leads (most likely candidates for further evaluation), and optimize leads i.e. transform biologically active compounds into suitable drugs by improving their physicochemical, pharmaceutical, ADMET/PK (pharmacokinetic) properties.

Virtual screening is used to discover new drug candidates from different chemical scaffolds by searching commercial, public, or private 3-dimensional chemical structure databases.

It is intended to reduce the size of chemical space and thereby allow focus on more promising candidates for lead discovery and optimization.

The goal is to enrich set of molecules with desirable properties (active, drug-like, lead-like) and eliminate compounds with undesirable properties (inactive, reactive, toxic, poor ADMET/PK).