Although it has been clearly established that a protein is able to undergo conformational changes during the binding process, most docking studies consider the protein as a rigid structure. The reason for this crude approximation is the extraordinary increase in computational complexity that is required to include the degrees of freedom of a protein in a modeling study. There is currently no computationally efficient docking method that is able to screen a large database of potential ligands against a target receptor while considering the full flexibility of both ligand and receptor. In order for this process to become efficient, it is necessary to find a representation for protein flexibility that avoids the direct search of a solution space comprised of thousands of degrees of freedom. What follows is a brief review of the different representations that have been used to incorporate protein flexibility in the modeling of protein/ligand interactions. A common theme behind all these approaches is that the accuracy of the results is usually directly proportional to the computational complexity of the representation. The different types of flexibility representations models are grouped into categories that illustrate some of the key ideas that have been presented in the literature in recent years. However it is important to note that the boundaries between these categories are not rigid and in fact several of the publications referenced below could easily fall in more than one category.
Flexibility representations
Soft receptors
Perhaps the simplest solution to represent some degree of receptor flexibility in docking applications is the use of soft receptors. Soft receptors can be easily generated by relaxing the high energy penalty that the system incurs when an atom in the ligand overlaps an atom in the receptor structure. By reducing the van der Waals contributions to the total energy score the receptor is in practice made softer, thus allowing, for example, a larger ligand to fit in a binding site determined experimentally for a smaller molecule (see Figure 6). The rationale behind this approach is that the receptor structure has some inherent flexibility which allows it to adapt to slightly differently shaped ligands by resorting to small variations in the orientation of binding site chains and backbone positions. If the change in the receptor conformation is small enough, it is assumed that the receptor is capable of such a conformational change, given its large number of degrees of freedom, even though the conformational change itself is not modeled explicitly. It is also assumed that the change in protein conformation does not incur a sufficiently high energetic penalty to offset the improved interaction energy between the ligand and the receptor. The main advantage of using soft receptors is ease of implementation (docking algorithms stay unchanged) and speed (the cost of evaluating the scoring function is the same as for the rigid case).
a) Three dimensional van der Walls representation of a target receptor. b) Close up image of a section of the binding site. For the purposes of rigid protein docking, the receptor is commonly described by the union of the volumes occupied by its atoms. The steric collision of any atom of the candidate ligand with the atoms of the receptor will result in a high energetic penalty. c) Same section of the binding site as shown in b) but with reduced radii for the atoms in the receptor. This type of soft representation allows ligand atoms to enter the shaded area without incurring a high energetic penalty.
Questions & Answers
A golfer on a fairway is 70 m away from the green, which sits below the level of the fairway by 20 m. If the golfer hits the ball at an angle of 40° with an initial speed of 20 m/s, how close to the green does she come?
A mouse of mass 200 g falls 100 m down a vertical mine shaft and lands at the bottom with a speed of 8.0 m/s. During its fall, how much work is done on the mouse by air resistance
Chemistry is a branch of science that deals with the study of matter,it composition,it structure and the changes it undergoes
Adjei
please, I'm a physics student and I need help in physics
Adjanou
chemistry could also be understood like the sexual attraction/repulsion of the male and female elements. the reaction varies depending on the energy differences of each given gender. + masculine -female.
Pedro
A ball is thrown straight up.it passes a 2.0m high window 7.50 m off the ground on it path up and takes 1.30 s to go past the window.what was the ball initial velocity
2. A sled plus passenger with total mass 50 kg is pulled 20 m across the snow (0.20) at constant velocity by a force directed 25° above the horizontal. Calculate (a) the work of the applied force, (b) the work of friction, and (c) the total work.
you have been hired as an espert witness in a court case involving an automobile accident. the accident involved car A of mass 1500kg which crashed into stationary car B of mass 1100kg. the driver of car A applied his brakes 15 m before he skidded and crashed into car B. after the collision, car A s
can someone explain to me, an ignorant high school student, why the trend of the graph doesn't follow the fact that the higher frequency a sound wave is, the more power it is, hence, making me think the phons output would follow this general trend?
Nevermind i just realied that the graph is the phons output for a person with normal hearing and not just the phons output of the sound waves power, I should read the entire thing next time
Joseph
Follow up question, does anyone know where I can find a graph that accuretly depicts the actual relative "power" output of sound over its frequency instead of just humans hearing
Joseph
"Generation of electrical energy from sound energy | IEEE Conference Publication | IEEE Xplore" ***ieeexplore.ieee.org/document/7150687?reload=true
A string is 3.00 m long with a mass of 5.00 g. The string is held taut with a tension of 500.00 N applied to the string. A pulse is sent down the string. How long does it take the pulse to travel the 3.00 m of the string?
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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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