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Formally, the protein-ligand docking problem is the following: We are given a geometric and chemical description of a protein and an arbitrary small organic molecule. We want to determine computationally whether the small molecule will bind to the protein, and if so, we would like to estimate the geometry of the bound complex, as well as the affinity of the binding. Most algorithms include two components: a search technique to find the optimal placement of the ligand in the binding pocket of the protein, and a scoring function to rate each placement, as well as to rank candidate ligands against each other. The remainder of this module will cover a range of docking approaches, starting with the simplest, rigid-receptor methods, which make very restrictive assumptions about the dynamics of the protein and candidate ligands, and then moving on to more complex approaches that allow the receptor to change conformation. The latter methods have the potential to identify ligands that might be missed by simpler approaches.

Trypsin, a protease involved in digestion (PDB structure ID 3ptb)
Benzamidine, a trypsin inhibitor (PDB structure ID 3ptb)
Stereo view of benzamidine (red) docked in the active site of trypsin (blue) (PDB structure ID 3ptb)

Components of a docking program

As stated earlier, protein-ligand docking methods generally consist of two components: a ligand placement algorithm to enumerate and test possible poses for the ligand in the protein's active site, and a scoring function to evaluate each placement, as well as to evaluate one candidate ligand against another. Each of these componets is introduced in more detail below.

Ligand placement algorithm

The first part of any docking technique is a method to place the ligand in various candidate poses in the binding pocket of the receptor. Although each placement could be completely random and independent, most algorithms either use heuristics based on the chemistry or geometry of the atoms involved (FlexX, DOCK), or use a standard optimization technique such as simulated annealing or a genetic algorithm (Autodock, Gold). A few use explicit molecular dynamics simulation.

Scoring function

The scoring function provides a way to rank placements of ligands relative to one another. Ideally, the score should correspond directly to the binding affinity of the ligand for the protein, so that the best scoring ligands are the best binders. Scoring functions generally fall into three categories:

Explicit force field scoring function

Modified versions of both the AMBER and CHARMM force fields (see this module for more on force fields) have been used as scoring functions. For some complexes, they have been found to provide a good approximation of the free energy of binding. Early versions of Autodock used a subset of the AMBER force field.

Empirical scoring functions

The score is expressed as a weighted sum: i i interactions ΔG i f i l, r where ΔG i is an empirically determined weight for the ith interaction type. It corresponds to the average free energy contribution of a single interaction of that type over the set of receptor-ligand systems used to normalize the scoring function. The types of interactions that might be included in an empirical scoring function include hydrogen bonds, electrostatic interactions, hydrophobic contacts, solvent exclusion volume, and electrostatic interactions, among others. Examples of empirical scoring functions include the Autodock 3.0 scoring function (see below), Protherics Inc.’s ChemScore [1] , and Boehm’s SCORE1 [2] .

Questions & Answers

Is there any normative that regulates the use of silver nanoparticles?
Damian Reply
what king of growth are you checking .?
What fields keep nano created devices from performing or assimulating ? Magnetic fields ? Are do they assimilate ?
Stoney Reply
why we need to study biomolecules, molecular biology in nanotechnology?
Adin Reply
yes I'm doing my masters in nanotechnology, we are being studying all these domains as well..
what school?
biomolecules are e building blocks of every organics and inorganic materials.
anyone know any internet site where one can find nanotechnology papers?
Damian Reply
sciencedirect big data base
Introduction about quantum dots in nanotechnology
Praveena Reply
what does nano mean?
Anassong Reply
nano basically means 10^(-9). nanometer is a unit to measure length.
do you think it's worthwhile in the long term to study the effects and possibilities of nanotechnology on viral treatment?
Damian Reply
absolutely yes
how to know photocatalytic properties of tio2 nanoparticles...what to do now
Akash Reply
it is a goid question and i want to know the answer as well
characteristics of micro business
for teaching engĺish at school how nano technology help us
Do somebody tell me a best nano engineering book for beginners?
s. Reply
there is no specific books for beginners but there is book called principle of nanotechnology
what is fullerene does it is used to make bukky balls
Devang Reply
are you nano engineer ?
fullerene is a bucky ball aka Carbon 60 molecule. It was name by the architect Fuller. He design the geodesic dome. it resembles a soccer ball.
what is the actual application of fullerenes nowadays?
That is a great question Damian. best way to answer that question is to Google it. there are hundreds of applications for buck minister fullerenes, from medical to aerospace. you can also find plenty of research papers that will give you great detail on the potential applications of fullerenes.
what is the Synthesis, properties,and applications of carbon nano chemistry
Abhijith Reply
Mostly, they use nano carbon for electronics and for materials to be strengthened.
is Bucky paper clear?
carbon nanotubes has various application in fuel cells membrane, current research on cancer drug,and in electronics MEMS and NEMS etc
so some one know about replacing silicon atom with phosphorous in semiconductors device?
s. Reply
Yeah, it is a pain to say the least. You basically have to heat the substarte up to around 1000 degrees celcius then pass phosphene gas over top of it, which is explosive and toxic by the way, under very low pressure.
Do you know which machine is used to that process?
how to fabricate graphene ink ?
for screen printed electrodes ?
What is lattice structure?
s. Reply
of graphene you mean?
or in general
in general
Graphene has a hexagonal structure
On having this app for quite a bit time, Haven't realised there's a chat room in it.
what is biological synthesis of nanoparticles
Sanket Reply
how did you get the value of 2000N.What calculations are needed to arrive at it
Smarajit Reply
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Source:  OpenStax, Geometric methods in structural computational biology. OpenStax CNX. Jun 11, 2007 Download for free at http://cnx.org/content/col10344/1.6
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