Ab Initio Protein Structure Prediction

Ab Initio Protein Structure Prediction

In both homology modeling and the threading template is used. The approach varies in both i.e with a single sequence and with a fold. These are used when there is some experimental data available.

When there is no experimental detail available to form any coordinates then certain laws are the mode in use established laws of Maths. Physics and Chemistry are utilized for building /predicting the 3-D structure of a protein. In terms of physical chemistry. the molecules with minimum energy are stable.

The questions which arise are

1. How to define protein-energy?
2. How to find the conformation for which the energy will be minimum?

There are many methods to deal with both of these questions. By answering one, answers for others will be obtained. Some methods use existing structural information as pseudo information. They form segments of protein structure. When they get some dipeptides, tripeptides, tetrapeptides, energies then they replace the energies with that of the calculated ones Identical sequence patch with the highest length. In this way, the sequence is converted into the structure. When such information is not available then laws are used. Different conformation structures are obtained. More than one combinations are also possible in case of making fragments.
 
Structure a    100 amino acids
Structure b    30 dipeptides, 40 tripeptides, 20 Penta, 10 Hexa.
Structure c     In some combination these may change
  
All combinations are taken. Their energies are calculated & then that with the lowest is selected. Thus, these methods use existing experimental. All possible angles are calculated, the more the dimensions, the more confirmations.

In energy calculating methods, the computational cost is a problem. So sometimes computational cost becomes very high especially in case of large proteins. Even supercomputers require time in this case such servers require a lot of time. The information applied here is obtained from NMR. There are also many methods that deviate from ab initio methods they are not 100% ab initio.

Energy calculation is called Global Minimum. The structure is plotted against, structure on the x-axis and energy on the y-axis. In the graph obtained, the lowest energy will have the deepest peak.

The structures obtained from NMR are considered to be in native form. In the case of x-ray crystallography, the proteins are crystallized whereas in the body protein is in a dynamic state. Proteins are dynamics not static whereas crystallography yields a static structure. But it is said regarding crystallography that out of all the conformations a protein has in the body it might be describing one. In NMR protein is in solution form & NMR comes in the form of a peak. The nuclear magnetic resonance property is used to make the structure.

In this case, the protein structure is dynamic i.e. more than one position of one atom at different time intervals & draw different conformations at different times. But a question arises that proteins perform a function in the presence of other atoms & proteins. Their invivo structures are determined by electron microscopy. So bioinformatics in this regard has half information from experiment & half computed through computational methods.
For example, in image processing, we colors combine to form a specific shade. Similar programs like these are used in bioinformatics. For this purpose, information from NMR & crystallography is considered as natural structures as they are experimentally determined.

There are different methods available that describe the dynamic nature of molecules by computer methods. AMBER (Assisted Model Building With Energy Refinement) force field calculation is done via Newton's Law of motion. How one atom can move and with what force & in which field will it move i.e force field. Thus, the dynamicity of either experimentally determined or predicted is seen for their dynamic conformations. Dynamicity values are given by some programs and out of these, a structure is determined.

I.TASEER                                    SEGMER                                                 Phyre

Lomets (threading method).

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