Methods for active site analysis of proteins??? 20

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The active site of an enzyme is usually a depression or fissure on the surface of the protein that allows the substrate to bind and intercalate, and the substrate usually binds to existing amino acids through different reactive binding sites, such as hydrogen bonds, ionic bonds, van der Waals force interactions, or dipole-dipole interactions. For example, the substrate may bind to serine residues by hydrogen bonding, suffocate to aspartic acid residues by ionic bonding, or van der Waals force binding to phenylcrylaminic acid residues.

These binding effects must be large enough for the substrate to bind adequately to the acceptor in the enzyme-catalyzed reaction, but once a product is formed, these binding effects are diminished to ensure that the product can be dissociated.

Due to the presence of an excess bonding reaction, the enzyme inhibitor can adhere to the binding site and lock the site, which is very important for the design of enzyme inhibitors.

It's hard to say everything about this.

Generally speaking, the first thing you should pay attention to is some special amino acids, such as acidic and alkaline amino acids, personal understanding, proteins and other substances, whether other proteins, or nucleic acids, etc., the main force is the force of positive and negative charges.

This is one of them. Second, I think sometimes we have to consider the problem of spatial conformation, the amino acid residues of different peptide chains may determine and affect each other in space, and I see that many active proteins, in the spatial conformation, sometimes basically form an electron-gaining amino acid-electron-losing amino acid-electron-gaining amino acid-such a spatial arrangement, which has completed a series of parallel spatial electron transport.

Or, you can look up this family of proteins, such as tyrosine kinase, and its active site must be related to butyric acid.

Select Compute PL MW on the right

Open the interface. Enter the name of the molecule, then.

Right to come out later.

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1 Active site analysis.

This method can be used to detect atoms or groups that interact well with the active sites of biological macromolecules. The probes used for analysis can be simple molecules or fragments, such as water or benzene rings, and by analyzing the interaction of the probes with the active site, it is possible to find the possible binding sites of these molecules or fragments in the active site. The information on receptor binding derived from active site analysis is instructive for the design of novel drugs.

Active site analysis software includes DRID, GREEN, HSITE, etc. In addition, there are some software based on Monte Carlo and simulated annealing technology, such as MCSS, HINT, buckets, etc.

Among them, the grid was developed by the Goodford research group, and its basic principle is to divide the active site of the receptor protein into regular grid points, place the probe molecule (water molecule or methyl group, etc.) on these grid points, and use the molecular force field method to calculate the interaction energy of the probe molecule and each atom at the active site of the acceptor, so as to obtain the distribution of the interaction between the probe molecule and the active site of the receptor, from which the optimal site of action can be found. The first example of GRID was to use a water molecule as a probe molecule to search for the binding site of water in the active site of dihydrofolate reductase (DHFR) and the hydrogen bonding site of the inhibitor. Among the drugs successfully designed by this software is the anti-type A cold virus drug 4guanidine-neu5ac2en (GG167, RelenzaTM).

The compound has a strong anti-cold virus ability, which overcomes the drug resistance defects of previous anti-cold virus drugs, and has a good market prospect.

MCSS is developed by Miranker and KarPlus on the basis of the Charmm force field, and its basic point is to eliminate the non-bonding interactions between solvent molecules when using the CharmM force field for molecular dynamics simulations. In this way, during molecular dynamics simulations, the solvents are superimposed in the energy-appropriate region, which improves the efficiency of searching for the region where the solvent molecule binds to the acceptor molecule. Small molecule fragments (such as water and benzene molecules) can be used as solvent molecules, and the above kinetic methods are used to search for the binding region between the molecular fragments and the acceptor, and then 100 1000 copies of each fragment are selected for energy optimization in the low-energy fragment binding domain.

In the final energy search process, it can be implemented by random sampling or grid points. During the search, each copy of each fragment can be rigidly rotated, and finally the binding energy of each copy of each fragment to the receptor can be directly compared, so as to select the best site of action of the fragment. In 2001, Adlington et al. used MCSS to analyze the active sites of prostate-specific immunogen (PSA) in detail, so as to optimize the structure of existing PSA inhibitors, so as to obtain the highest active PSA inhibitor so far.

When using the docking module in DS for docking research, there are generally several methods for the selection of active sites. First of all, it is completely dependent on DS software according to the nature of the compound you want to study, there is DS to complete the guessing of the active site, what is the specific process, you can take a good look at the description part of the DS to find the active site (Find Active Site), after this operation, you will get many groups of active sites, and then combine your own understanding of the active site of this compound (generally ** in the reading of the literature), select the active site you want, docking. The second method is that you have a deep understanding of the compound to be docked, and it is clearly stated in the literature that one or several residues are the key residues that make up the active site.

In this way, you can select these amino acid residues, and then use them as active sites to define the docking ball, so that you can perform the next docking calculation.