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Alternative conformations for HIV-1 protease. Tube representation of HIV-1 protease (PDB codes 4HVP and 1AID) bound to different inhibitors represented by spheres. The plasticity of the binding site of the protein allows the protease to change its shape in order to accommodate ligands with widely different shapes and volumes.

Applying the PCA procedure as outlined before to a set of HIV-1 samples from simulation produces 1,782-dimensional principal components. Since the physical interpretation of the PCs is quite intuitive in this case, the PC coordinates can be split in groups of 3 to obtain the (x,y,z) components for each of the 594 atoms. These components are 3-dimensional vectors that point in the direction each atom would follow along the first PC. In figure 6 a), the per-atom components of the first PC have been superimposed in purple.

First mode of motion for the HIV-1 protease. a) The purple arrows are a convenient representation of the first PC grouped every 3 coordinates -(x,y,z) for each atom- to indicate the linear path each atom would follow. Note that the "flaps" have the most important motion component, which is consistent with the simulation data. b) A reference structure (middle) can be interpolated along the first PC in a negative direction (left) or a positive one (right). Using only one degree of freedom, the flap motion can be approximated quite accurately.

Figure 6 b) shows the effect of interpolating HIV-1 conformations along the first PC, or first mode of motion. Starting from an aligned conformation from the original data set, multiples of the first PC can be added to produce interpolated conformations. Note that the first mode of motion corresponds mostly to the "opening" and "closing" of the flaps, as can be inferred from the relative magnitued of the first PC components in the flap region. Thus, interpolating in the direction of the first PC produces an approximation of this motion, but using only one degree of freedom. This way, the complex dynamics of the system and the 1,782 apparent degrees of freedom have been approximated by just one, effectively reducing the dimensionality of the representation.

The residual variance (solid line) and percentage of overall variance explained (dashed line) after each principal component.

Figure 7 (solid line) shows the residual variance left unexplained by discarding the lower-ranked principal components. Residual variance plots always decrease, and in this case, the first PC accounts for approximately 40% of the total variance along the motion (the dashed line shows the percentage of total variance explained up to the given PC). Also, the first 10 PCs account for more than 70% of the total data variance. Given the dominance of only a few degrees of freedom it is possible to represent the flexibility of the protein in a drastically reduced search space.

Non-linear methods

PCA falls in the category of what is called a linear method, since mathematically, the PCs are computed as a series of linear operations on the input coordinates. Linear methods such as PCA work well only when the collective atom motions are small (or linear), which is hardly the case for most interesting biological processes. Non-linear dimensionality reduction methods do exist, but are normally much more computationally expensive and have other disadvantages as well. However, non-linear methods are much more effective in describing complex processes using much fewer parameters.

Questions & Answers

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.
Damian
yes that's correct
Professor
I think
Professor
what is the stm
Brian Reply
is there industrial application of fullrenes. What is the method to prepare fullrene on large scale.?
Rafiq
industrial application...? mmm I think on the medical side as drug carrier, but you should go deeper on your research, I may be wrong
Damian
How we are making nano material?
LITNING Reply
what is a peer
LITNING Reply
What is meant by 'nano scale'?
LITNING Reply
What is STMs full form?
LITNING
scanning tunneling microscope
Sahil
how nano science is used for hydrophobicity
Santosh
Do u think that Graphene and Fullrene fiber can be used to make Air Plane body structure the lightest and strongest. Rafiq
Rafiq
what is differents between GO and RGO?
Mahi
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
Rafiq
if virus is killing to make ARTIFICIAL DNA OF GRAPHENE FOR KILLED THE VIRUS .THIS IS OUR ASSUMPTION
Anam
analytical skills graphene is prepared to kill any type viruses .
Anam
what is Nano technology ?
Bob Reply
write examples of Nano molecule?
Bob
The nanotechnology is as new science, to scale nanometric
brayan
nanotechnology is the study, desing, synthesis, manipulation and application of materials and functional systems through control of matter at nanoscale
Damian
Is there any normative that regulates the use of silver nanoparticles?
Damian Reply
what king of growth are you checking .?
Renato
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
?
Kyle
yes I'm doing my masters in nanotechnology, we are being studying all these domains as well..
Adin
why?
Adin
what school?
Kyle
biomolecules are e building blocks of every organics and inorganic materials.
Joe
anyone know any internet site where one can find nanotechnology papers?
Damian Reply
research.net
kanaga
sciencedirect big data base
Ernesto
Introduction about quantum dots in nanotechnology
Praveena Reply
hi
Loga
what does nano mean?
Anassong Reply
nano basically means 10^(-9). nanometer is a unit to measure length.
Bharti
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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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