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This module introduces students to a family of algorithms for assessing molecular shape, volume, surface area, and negative space (i.e., pockets and cavities).

    Topics in this module

  • Introduction
  • Representing Shape
  • Alpha-Shapes
    • Delaunay Triangulation
    • Weighted Alpha-Shapes
  • Calculating Molecular Volume Using Alpha-Shapes
  • Related Software


Many problems in structural biology, require a researcher to understand the shape of a protein. At first glance, this may seem obvious. By opening a molecular visualizer, one can easily see the shape of a protein. But what about calculating the surface area or volume of the protein? What about performing analyses of the surface, such as looking for concave pockets in a protein that might be binding sites for other molecules? What about calculating the volume and shape of those empty binding pockets, in order to find molecules that might fit in them? What about determining whether a particular small molecule can fit in a binding pocket?

All of these problems require some formal notion of the shape of a protein. A protein structure file usually provides no more information than a list of atom locations in space and their types. It will be assumed that for any given application, a radius may be defined for each atom type. This leads to the space filling representation of a protein, in which each atom is treated as an impenetrable sphere.

Hiv-1 protease

A space filling representation of HIV-1 protease (yellow) with an inhibitory drug (red) blocking its binding site.
This representation allows for visualization, but it brings us no closer to being able to computationally decide which parts of which atoms are on the surface of the protein and which are buried inside the structure. Some additional tool is needed to capture notions of interior and exterior and spatial adjacency.

Representing shape

Using the sphere model for atoms, one way to define the shape of a molecule is as the union of (possibly overlapping) balls in R 3 .

Space filling diagram

The space filling diagram models each atom as a sphere in 3D.
Since proteins inside our cells are in an aqueous environment, considering a protein's interactions with solvent molecules, particularly water, is very important forappropriately modeling them. Recall that one of the phenomena that determines the structure of a protein is the hydrophobic effect: some amino acid residues are stabilized by the presence of water, and others are repelled. The extent of the interaction of a protein with the surrounding waterdepends on the surface area of the protein that can be reached by water molecules. Therefore, quantitave modeling of the strength of interaction with solvent often involves computing the solvent accessible surface area (SASA) . Computing SASA can be done by regarding each solvent molecule as a sphere of set radius. This is of course a simplification, since water molecules are not spherical. When thissphere rolls about the molecule, its center delineates the SASA. One can think of the SASA of a molecule as the result of growing each atom sphere bythe radius of the solvent sphere. Instead, by taking what is swept out by the front of the solvent sphere, we obtain the molecular surface (MS) model of the molecule. Alternatively, the MS can be obtained by removing a layer ofsolvent radius depth from the SASA model.

Representations of molecular shape

Vdw representation

Each atom can be modeled as a Van der Waals sphere in three dimensions. The union of the spheres gives the molecular surface.

Accessible surface area

Not all molecular surface is accessible to solvent due to the existence of small cavities. Rolling a solvent ball over the Van der Waalsspheres traces out the surface area experienced by the solvent. Solvent accessible surface area (SASA) is a very important measure forquantitatively determining the behavior and interaction tendencies of a protein.
Two different notions and representations of the surface of a molecule.
The surface determined by SASA analysis depends on the size of a typical solvent molecule. The larger the solvent, the less contoured the resulting surface will appear, because a larger probe molecules would not be able to fit into some of the interatomic spaces that a smaller one would.

Solvent accessible surface area

Probing the surface area with a solvent ball of radius 1.4 å

Typically, solvent is modeled as a ball of radius 1.4 Å. This delineates the solvent accessible surface shown.

Probing the surface area with a solvent ball of radius 1.5 å

Increasing the radius of the solvent ball reduces the solvent accessible surface area because there are more cavitiesthat a bulkier ball cannot penetrate.
Solvent-accessible surface area (SASA) for two different solvent radii.

Questions & Answers

where we get a research paper on Nano chemistry....?
Maira Reply
what are the products of Nano chemistry?
Maira Reply
There are lots of products of nano chemistry... Like nano coatings.....carbon fiber.. And lots of others..
Even nanotechnology is pretty much all about chemistry... Its the chemistry on quantum or atomic level
no nanotechnology is also a part of physics and maths it requires angle formulas and some pressure regarding concepts
Preparation and Applications of Nanomaterial for Drug Delivery
Hafiz Reply
Application of nanotechnology in medicine
what is variations in raman spectra for nanomaterials
Jyoti Reply
I only see partial conversation and what's the question here!
Crow Reply
what about nanotechnology for water purification
RAW Reply
please someone correct me if I'm wrong but I think one can use nanoparticles, specially silver nanoparticles for water treatment.
yes that's correct
I think
Nasa has use it in the 60's, copper as water purification in the moon travel.
nanocopper obvius
what is the stm
Brian Reply
is there industrial application of fullrenes. What is the method to prepare fullrene on large scale.?
industrial application...? mmm I think on the medical side as drug carrier, but you should go deeper on your research, I may be wrong
How we are making nano material?
what is a peer
What is meant by 'nano scale'?
What is STMs full form?
scanning tunneling microscope
how nano science is used for hydrophobicity
Do u think that Graphene and Fullrene fiber can be used to make Air Plane body structure the lightest and strongest. Rafiq
what is differents between GO and RGO?
what is simplest way to understand the applications of nano robots used to detect the cancer affected cell of human body.? How this robot is carried to required site of body cell.? what will be the carrier material and how can be detected that correct delivery of drug is done Rafiq
analytical skills graphene is prepared to kill any type viruses .
Any one who tell me about Preparation and application of Nanomaterial for drug Delivery
what is Nano technology ?
Bob Reply
write examples of Nano molecule?
The nanotechnology is as new science, to scale nanometric
nanotechnology is the study, desing, synthesis, manipulation and application of materials and functional systems through control of matter at nanoscale
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.
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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