#Pharmacophore Modelling Drug Design # BIOVIA DRUG DISCOVERY#Discovery Studio#Pharmacophore Modeling

FUNDAMENTALS OF DRUG DISCOVERY, Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target.[1] The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most 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. Drug design frequently but not necessarily relies on computer modeling techniques.[2] [3] This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design.[3] In addition to small molecules, biopharmaceuticals including peptides[4][5] and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.[6] The phrase "drug design" is to some extent a misnomer. A more accurate term is ligand design (i.e., design of a molecule that will bind tightly to its target).[7] Although design techniques for prediction of binding affinity are reasonably successful, there are many other properties, such as bioavailability, metabolic half-life, side effects, etc., that first must be optimized before a ligand can become a safe and efficacious drug. These other characteristics are often difficult to predict with rational design techniques. Nevertheless, due to high attrition rates, especially during clinical phases of drug development, more attention is being focused early in the drug design process on selecting candidate drugs whose physicochemical properties are predicted to result in fewer complications during development and hence more likely to lead to an approved, marketed drug.[8] Furthermore, in vitro experiments complemented with computation methods are increasingly used in early drug discovery to select compounds with more favorable ADME (absorption, distribution, metabolism, and excretion) and toxicological profiles, A biomolecular target (most commonly a protein or a nucleic acid) is a key molecule involved in a particular metabolic or signaling pathway that is associated with a specific disease condition or pathology or to the infectivity or survival of a microbial pathogen. Potential drug targets are not necessarily disease causing but must by definition be disease modifying.[10] In some cases, small molecules will be designed to enhance or inhibit the target function in the specific disease modifying pathway. Small molecules (for example receptor agonists, antagonists, inverse agonists, or modulators; enzyme activators or inhibitors; or ion channel openers or blockers)[11] will be designed that are complementary to the binding site of target.[12] Small molecules (drugs) can be designed so as not to affect any other important "off-target" molecules (often referred to as antitargets) since drug interactions with off-target molecules may lead to undesirable side effects.[13] Due to similarities in binding sites, closely related targets identified through sequence homology have the highest chance of cross reactivity and hence highest side effect potential.Most commonly, drugs are organic small molecules produced through chemical synthesis, but biopolymer-based drugs (also known as biopharmaceuticals) produced through biological processes are becoming increasingly more common.[14] In addition, mRNA-based gene silencing technologies may have therapeutic applications.[15] Rational drug discovery
In contrast to traditional methods of drug discovery (known as forward pharmacology), which rely on trial-and-error testing of chemical substances on cultured cells or animals, and matching the apparent effects to treatments, rational drug design (also called reverse pharmacology) begins with a hypothesis that modulation of a specific biological target may have therapeutic value. In order for a biomolecule to be selected as a drug target, two essential pieces of information are required. The first is evidence that modulation of the target will be disease modifying. This knowledge may come from, for example, disease linkage studies that show an association between mutations in the biological target and certain disease states.[16] The second is that the target is "druggable". This means that it is capable of binding to a small molecule and that its activity can be modulated by the small molecule.[17]Once a suitable target has been identified, the target is normally cloned and produced and purified.

[hennysriwahyuni]

Hello sir, I hope you are doing well. Could you give me a step-by-step from first how to do pharmocopore modelling and how to make the structure from pharmacophore modelling results? Thank you

[apoorvamkulkarni]

how can the pharmacophore be generated only with the protein structure assuming we know the active site residues but have no ligand-protein structure

[yasrafatima]

hello sir! hope you are doing well ! sir i don't have an access to generate pharmacophore automatically i have discovery studio installed in my laptop but dont have automatics pharmacophore generation in that . kindly tell me what to do

[elainejoytorre]

is this ligand-based or structure-based pharmacophore modelling? Having a hard time differentiating the two. Thank you

[saramahrouk]

When I try to display a 2D diagram of the ligand in Discovery Studio, I receive an error message saying 'Ligand is not a single fragment' and I don't know what I need to do. I need help to resolve this issue.

[jahangirahmed]

How to make ligand library in discovery studio and how to check error in those small molecule preprocessing steps

[veenasukumaren]

Sir, is there any validation step required after performing this experiment.

[uzmazeeshan]

THANKS FOR EXPLAINING THE EVERY STEP IN DETAIL. I HAVE DISCOVERY STUDIO SOFTWARE BUT CAN'T ABLE TO ACCESS TO ADDITIONAL FEATURES DUE TO UNAVAILABILITY OF SERVER. CAN YOU GUIDE ME IN THIS SCENARIO FOR SOLVING THIS ISSUE, KINDLY PROVIDE ME YOUR EXPERT OPINION

[bharatsahu]

THANKU SIR, I HOPE YOU DOING WELL SIR

[AbdulrahmanMSaleh]

Great . Can you send me the liscence of biovia discovery studio