Homology Modeling Service

The homology modeling method is the most widely used protein prediction method. Homology modeling predicts the three-dimensional structure of target proteins based on template proteins. For proteins without experimental crystal structures, homology modeling is undoubtedly an important and effective auxiliary method. The constructed protein model can also be used for subsequent molecular mechanism exploration. Source modeling is a practical method for predicting structure from sequences. There are two prerequisites for this method: First, there are one or several distinguishable structures in the homologous protein of the target sequence. Second, the homology between the target sequence and the protein is high.

Overall solution

• Select template and alignment sequence: Search for template proteins with known crystal structure from protein database and use BLAST and other tools to align sequences;
• Determine whether there is a template available: template sequence and target sequence similarity> 30 %;
• Build the main chain structure: apply the atomic coordinates of the template structure to the target to generate the basic main chain skeleton and then adjust the main chain atom position to make the bone structure conform to the principle of stereochemistry;
• Build the ring area: One method is to model based on known ring structure. Another method is to predict from scratch based on the principles of quantum chemistry;
• Modeling and optimization of the side chain: use target sequence fragments to search the rotamer database to obtain similar fragments, and then construct the side chain structure of this fragment according to its spatial orientation Finally, the energy is minimized to find the lowest energy point, that is, the stable conformation;
• The overall structure is optimized: there is usually unreasonable contact between atoms in the three-dimensional model obtained through the above process, which needs to be eliminated by methods such as simulated annealing and molecular dynamics.
• Structural evaluation: The most common evaluation standard is RMSD, which represents the root-mean-square deviation of the corresponding atoms between the target protein and the template protein. It can also be submitted to the SAVES server for verification.

Our homology modeling services

CD ComputaBio provides high-quality homology modeling services. The results can help researchers understand the structural properties of the target protein, analyze its "structure-function" relationship, and can be used for drug screening, discovery of potential therapeutic drugs for a disease, or study the interaction between the target and drug. If you need protein structure modeling service, please feel free to contact us.

Advantages for our homology modeling services:

Homology modeling is a general term for the conversion of primary sequences into 3D structures based on template proteins. It is currently the most effective method for protein three-dimensional structure prediction, and is widely used because of its simplicity, efficiency and high accuracy. According to the theory that the conservativeness of the three-dimensional structure of homologous proteins exceeds the protein sequence, under the premise that the identity of the protein sequence is greater than 30%, proteins with unknown structures can use one or more related structures to construct their three-dimensional structure. We provide a variety of protein structure modeling, but not limited to:

• Fold recognition services
• Antibody modeling services 
• Fusion Protein Modeling Service
• Membrane protein modeling services

• • Q: What is the basic assumption of homology modeling?

    • A: If there is sequence, structural and functional homology between an unknown structural protein A and a known structural protein B, then protein A can be used as a template for protein B to build its all-atomic three-dimensional structure. Protein 3D structures are an important basis for understanding their biological functions and for structure-based drug design. With the rapid development of structural biology, the speed of measuring protein 3D structures using methods such as NMR or X-Ray crystallography has been greatly improved. However, the 3D structures of some proteins are still difficult to determine due to many reasons, such as excessive molecular weight or difficulty in crystallization. Such scenarios necessitate the use of computational simulations to construct the three-dimensional structures of proteins. Among the many computer modeling methods, homology modeling is one of the most technically mature, accurate and reliable means.

  • Q: What are the advantages of homology modeling?

    • A: Prediction is divided into ab initio prediction and homology modeling. The accuracy of homology modeling prediction is higher than that of ab initio prediction, although it is still not as accurate as the real measurement. By analyzing the predicted structures, many information can be obtained, such as explaining the catalytic mechanism of enzymes or predicting the mutation sites of proteins, inferring the relationship between protein structure and function, etc.

  • Q: How to place an order for homology modeling?

    • A: If the modelling needs are clear, you can make an appointment directly on the CD ComputaBio website by selecting the appropriate project. When making an appointment, you need to fill in the specific modelling requirements and provide the protein sequence. If you are not sure about the content of the calculation, you can contact the staff directly to communicate your requirements.

  • Q: What can you do with homology modeling?

    • A: We provide high-quality homology modeling services, the results of which can help researchers understand the structural properties of target proteins and analyze their "structure-function" relationships, and can be used for drug screening, discovering potential therapeutic agents for a disease, or studying the interaction patterns of targets and drugs.

  • Q: What type of data will I receive?

    • A: We will send you the raw data for homology modeling, the original optimized protein structure (pdb file), the optimized protein structure (pdb file), the data analysis results and related image analysis, and the result analysis.

  • Q: What is the basic process of homology modeling?

    • A: Homology modeling include the following process:

      Sequence search (query) to obtain homologous proteins of known structure as template proteins.

      Multiple sequence alignment (MSE) to determine the structurally conserved regions (SCRs) and the corresponding framework structure of the homologous protein.

      Construction of the three-dimensional structure of the target protein, including modeling of the main chain, side chain and loop region, usually by copying the backbone, constructing side chains, completing missing residues and optimizing the loop region (usually requiring iterative debugging).

      Energy minimization (usually an iterative process).

      Structural soundness assessment (evaluation).
  • Q: What are the common software used for homology modeling?

    • A:

      Swiss-Model: This is one of the most widely used tools by non-professionals and is characterized by its simplicity, automation and free of charge for academic teams.

      Modeller: Modeller was developed by Sali lab, is a very popular homology modeling tool that runs under window and linux operating systems. Modeller can perform multimer modeling, disulfide bond modeling, heteroatom modeling, etc. It comes with a structure evaluation system. The tool is controlled entirely from the command line and is slightly complicated to operate.

      Yasara: a commercially available and versatile software that includes homology modeling modules inside.