What is SCORE: - An Algorithm for Locating Nonoverlapping Regions of Maximum Alignment Score. It is used to calculate the binding affinity score. It is an empirical procedure to estimate the binding free energy of a ligand molecule to its receptor protein when the three dimensional structure of the protein is known.

The Binding affinity (∆G_bind) is the sum of vanderwaals’s interaction (∆G_vdw), hydrogen bonding (∆G_H-bond), hydrophobic interaction (∆G_hydrophobic), and the loss of entropy (∆G_rotor) due to freezing of rotatable bonds in the ligand.

(∆G_bind) = (∆G_vdw) + (∆G_H-bond) + (∆G_hydrophobic) + (∆G_rotor) + (∆G₀) where (∆G₀) is a constant.

What is CalP: - CalP is a program / Algorithm for the prediction of the octanol/water partition coefficients of organic compounds. The octanol/water partition coefficient is the most popular measure of the hydrophobicity / hydrophilicity of organic compounds. Usually it is the required quantity for legal issues e.g. concerning toxicity (the more hydrophobic a compound, the more easily is its uptake in (human) fat).

Also it is a good measure of the solubility in water and organic compounds, although also other factors (e.g. the stability of the crystalline material) play a major role.

What is LogP: - Octanol-water partition coefficient logP is used in QSAR studies and rational drug design as a measure of molecular hydrophobicity. Hydrophobicity affects drug absorption, bioavailability, hydrophobic drug-receptor interactions, metabolism of molecules, as well as their toxicity.

What is Log: -It is the logarithmic value of any given numeric value.

What is a Scoring Function :- (also cost function or weight function.) The score of an alignment of two sequences (a, b) is the sum of the score of all the replacement operations that lead from a to b.

What is Toxicity: - Toxicity is a measure of the poisoning strength of a chemical. In Biology toxicity can be defined as the ill effect produced by a drug molecule when it is administered to a living being.

What is a Pharmacophore: - A pharmacophore is a three-dimensional substructure of a molecule that carries (phoros) the essential features responsible for a drug's (pharmacon) biological activity. Alternatively it can be described as an ensemble of interactive functional groups with a defined geometry.

What is an Agonist: - An agonist is a drug which binds to a receptor and activates it, producing a pharmacological response (e.g. contraction, relaxation, secretion, enzyme activation, etc.). An antagonist is a molecule that improves the activity of a different molecule; e.g., a hormone, which acts as an agonist when it binds to its receptor, thus triggering a biochemical response.

What is an Antagonist – An antagonist is a drug which attenuates or reduces the effects of an agonist. Antagonism can be competitive and reversible (i.e. it binds reversibly to a region of the receptor in common with the agonist.) or competitive and irreversible (i.e. antagonist binds covalently to the agonist binding site, and no amount of agonist can overcome the inhibition). Other types of antagonism are non-competitive antagonism where the antagonist binds to an allosteric site on the receptor or an associated ion channel. An antagonist is a molecule that blocks the ability of a given chemical to bind to its receptor, preventing a biological response.

What is ED₅₀:- Effective dose - The ED50 (Effective Dose 50) is the amount of material required to produce a specified effect in 50% of an animal population.

What is LD₅₀:- Lethal Dose - LD50: (Lethal Dose 50) is the dose of a chemical which kills 50% of a sample population.

What is EC₅₀:- Effective Concentration - The molar concentration of an agonist, which produces 50% of the maximum possible response for that agonist.

What is IC₅₀:- Inhibitory Concentration - The molar concentration of an agonist, which produces 50% of the maximum possible inhibitory response for that agonist.

What are Hydrophobic and Hydrophilic Groups: - They can be defined as follows: -

Hydrophilicity: - It is a characteristic of materials exhibiting an affinity for water. Hydrophilic literally means "water-loving" and such materials readily adsorb water. The surface chemistry allows these materials to be wetted forming a water film or coating on their surface. Hydrophilic materials also possess a high surface tension value and have the ability to form "hydrogen-bonds" with water.

Hydrophobicity: - These are the materials possessing this characteristic have the opposite response to water interaction compared to hydrophilic materials. Hydrophobic materials ("water hating") have little or no tendency to adsorb water and water tends to "bead" on their surfaces (i.e., discrete droplets). Hydrophobic materials possess low surface tension values and lack active groups in their surface chemistry for formation of "hydrogen-bonds" with water.

What is rendering: - Viewing the three dimensional structure of molecules in different way for example (ball and stick model, wires, space fill, backbone, strands, ribbons, cartoon etc). In CalTool we have incorporated a 3 dimensional viewer which allows the user to visualize the protein and ligand molecules in different ways of rendering.

What is PoLoC*: - This program helps to localize and pinpoint the probable active sites of a protein. With the help this program when a protein molecule is given as input in the PDB format, PoLoC searches for the predicts the probable active sites on the protein and lists them so that the user can use his discretion to mark the active site with the help of which view them in the 3D viewer which is an integral part of CalTool.

What is CalTool*: - This is the CalTrone BioSofT Private Limiteds’ tool for performing Structure Based Drug Designing.

It incorporates a 3D molecule viewer* with enhanced features to view the protein molecules in the form of strands, ball and stick model, spacefiller model, backbone model, ribbons etc.

It has the options to view the predicted active sites of the protein molecule using the tool – PoLoC*.

The Ligand building tool called as DeLigner* enables the user to develop drug molecules by either the growth strategy, or the linking strategy or by the mutating strategy.

The DeLigner* takes the input in the form of a protein as a pdb file and the maps the active site in the protein as input by the user. Then it generates the interaction sites within the active site in order to start the building up of the pharmacophore models which in turns help in generating the ligand molecules considering all the user assigned parameters as well as the constraints which are provided by a fitness function incorporated in a genetic algorithm. This helps to avoid the chance of a combinatorial explosion thus improvising the process of drug discovery in silico.

What are Lipinski’s Rules: - molecular weight is more than 500, logP is over 5, there are more than 5 H- Bond donors, there are more than 10 H-Bond acceptors, in a drug molecule

What is Molecular weight: - The sum total weight of all the atoms present in the Drug/ligand molecule.

What is a Functional Group: - It’s the group which decides the nature of the molecule. For e.g. – COOH – carboxyl/acidic group, C=O – Carbonyl group

What is an Amino Acid: - Building blocks of peptides/polypeptides/proteins, consist of an amino terminal and a carboxyl group

What is a Chemical Score: - Chemical scoring allows the energy scoring function to be further tailored to enhance recognition of chemical complementarity. The attractive portion of the VDW term can often dominate the energy for uncharged molecules. With chemical scoring this term is scaled depending on the chemical labels assigned to the interacting atoms. It is activated by the chemical score parameter

Chemical scoring can be used to incorporate qualitative aspects of solvation. For instance hydrophobic-polar interactions can be made non-attractive or even repulsive. Further, it can be used to screen for molecules that contain a particular functional group (in concert with Chemical Matching) for presentation to a receptor active site

Chemical scoring is used for intermolecular scoring only. If intramolecular score is requested, then the regular energy score is computed for internal energy.

What is Systematic Sampling: - It’s a statistical approach where in the targets are selected from the large population of molecules generated. The main use of this approach is to see if the process has any variations due to different reasons. Systematic energy sampling is, in principle, the most thorough method for searching conformational energy space. The energy is sampled over the entire range of each degree of freedom (typically bond rotations) at regularly spaced intervals. The sampled conformations thus lie on an n-dimensional lattice (n being the number of degrees of freedom).

What is a Conformer: - One of a set of stereoisomers, each of which is characterized by a conformation corresponding to a distinct potential energy minimum

What is Conformational Search: - Proteins can assume different spatial arrangements (conformations) which differ by rotation about single bonds.  Conformational searches often involve generating many starting conformations and then carrying out energy minimization

What is a Pharmacophore Mod: - It refers to a pharmacophore model

What is an Elitism Ratio: - it is the ratio of the top molecules belonging to the old population to the total population of that generation of molecules. Elitism ensures that the best members in the old population will not lose unless they are replaced by better candidates.

What is Sybyl Mol2: - A mol2 file (.mol2) is a complete, portable representation of a SYBYL molecule. It is an ASCII file which contains all the information needed to reconstruct a SYBYL molecule.

What is PDB: Brookhaven Protein Data Bank; a database and format of files, which describe the 3D structure of a protein or nucleic acid, as determined by X-ray crystallography or nuclear magnetic resonance (NMR) imaging. The molecules described by the files are usually viewed locally by dedicated software, or can be visualized on the World Wide Web as *.pdb file format.

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