<< Chapter < Page Chapter >> Page >

Scoring function

FlexX uses a variant of the SCORE1 scoring function developed by Hans-Joachim Boehm for the de novo enzyme inhibitor design package LUDI. The scoring function has the following form:

Where f is a penalty function for deviations from ideal geometry for each kind of interaction, and f* is a function penalizing for lipophilic interactions deviating from an ideal separation distance.

Dock

Dock 1.0, first described in 1982 [8] , was the first automated receptor-ligand docking program. It was developed in the Department of Pharmacology at the University of California at San Francisco. Dock 4.0, the current version, was released in 1997 [9] .

Search technique

Like FlexX, Dock is driven by the geometry of the ligand and active site. The program approximates the shape of the binding cavity of the receptor with spheres. It then attempts to match the ligand to some subset of the centers of these spheres. Early versions used geometric hashing (see this module, covering local alignment methods ) to perform this matching, but more recent versions use bipartite graph matching (version 3.5) and single graph matching (version 4.0) for improved speed.

Scoring function

Dock offers three scoring functions. The first is based on an approximation to the Lennard-Jones potential (Van der Waals interactions). This essentially enforces geometric alignment and shape constraints. The second uses the program DELPHI to calculate the electrostatic potential of the complex.The third calculates the energy of the complex under the AMBER force field.

Flexible receptor docking

Introduction

As previously mentioned, docking entails determining not only the identity and three dimensional structure of the bound ligand, but also how the binding process affects the conformation of the receptor. This section will review the different receptor flexibility representations that have been proposed to study receptor conformational changes in the context of structure based drug design.

A central paradigm which was used in the development of the first docking programs was the lock-and-key model first described by Fischer [10] . In this model the three dimensional structure of the ligand and the receptor complement each other in the same way that a lock complements a key. However, further work confirmed that the lock-and-key model is not the most correct description for ligand binding. A more accurate view of this process was first presented by Koshland [11] in the induced fit model. In this model the three dimensional structure of the ligand and the receptor adapt to each other during the binding process. It is important to note that not only the structure of the ligand but also the structure of the receptor changes during the binding process. This occurs because the introduction of a ligand modifies the chemical and structural environment of the receptor. As a result, the unbound protein conformational substates, corresponding to the low energy regions of the protein energy landscape are likely to change. The induced fit model is supported by multiple observations in different proteins such as streptavidin, HIV-1 protease, DHFR, aldose reductase and many others.

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
how did you get the value of 2000N.What calculations are needed to arrive at it
Smarajit Reply
Privacy Information Security Software Version 1.1a
Good
Got questions? Join the online conversation and get instant answers!
Jobilize.com Reply

Get the best Algebra and trigonometry course in your pocket!





Source:  OpenStax, Geometric methods in structural computational biology. OpenStax CNX. Jun 11, 2007 Download for free at http://cnx.org/content/col10344/1.6
Google Play and the Google Play logo are trademarks of Google Inc.

Notification Switch

Would you like to follow the 'Geometric methods in structural computational biology' conversation and receive update notifications?

Ask