Creative BioMart is a well-known expert in the development of a variety of computational analysis methods to predict the three-dimensional structure of proteins, and predict its functional conformation from the amino acid sequence of the protein. With years of experience, we provide customized homology modeling service to precisely meet customer requirements.

Introduction of Homology Modeling

Homology modeling, also known as comparative modeling of proteins, is the computational process of constructing the three-dimensional atomic-resolution structure of a "target" protein of unknown structure. The novel structure of the target protein is modeled using its own amino acid sequence and the known experimental structure of the homologous protein as templates for model building. Generally speaking, the process of homology modeling consists of four steps: target identification, sequence alignment, model construction and model refinement. For example, researchers have used homology modeling to overcome various problems in the crystallization of membrane proteins involved in major disease-related pathways, providing a higher level of understanding of receptor-ligand interactions.

The homology modeling routine requires three inputs:

(1) The sequence of a protein with an unknown 3D structure, the "target sequence".

(2) 3D templates are selected by having the highest sequence identity to the target sequence. The 3D structure of the template must be determined by reliable empirical methods such as crystallography or NMR, and is usually a published atomic coordinate "PDB" file from a protein database.

(3) Alignment between target sequence and template sequence.

Fig 1. Steps in homology model building process. (Sliwoski G, et al., 2014)

Services

Assuming you have not empirically solved the 3D structure of the target protein by X-ray crystallography or NMR, currently only the protein sequence. This gives you the option of homology modeling. As a leading service provider of protein engineering, Creative BioMart's scientists have become familiar with the methods of homology modeling, providing you with useful structural models for generating hypotheses about protein function and guiding further experimental work.

Generally speaking, the process of homology modeling consists of four steps: target identification, sequence alignment, model construction and model refinement. We provide you with one-stop service for homology modeling:

• Target sequence selection: we will help you choose according to your needs. In some cases, instead of modeling the entire protein, you can select the necessary protein sequences or domains.
• Template protein identification: we use simple sequence alignment software to match your protein of interest to all related protein structures present in various databases. Choose the protein most closely related to your target to use as a template structure.
• Preparation of template protein: we help you trim other foreign substances (such as symmetrically equivalent protein chains, water molecules, ligands and crystallization solvents) contained in the template protein.
• Sequence alignment: we use sequence alignment tools (such as CustalW) to align your target and template protein sequences. Tells you which parts have fully conserved amino acid sequences by comparing all proteins, targets and templates.
• Secondary structure prediction: we use tools in ExPASy Portal to build secondary structure models.
• Tertiary structure and preliminary model: we piece together the secondary structure elements that build the model to predict the tertiary structure of the target and examine its overall structure to ensure it is reasonable.
• Loop modeling: we use loop modeling software like Modloop to do this and improve the quality of the final model.
• Model optimization and validation: we use protein model validation tools and validation servers to validate that your protein models are energetically satisfactory, as well as conformational distributions.

We consider homology modeling methods only when there are proteins with experimental structures (more than 30% sequence identity) that you suspect are similar to your target protein. It relies on programs such as BLAST to search various databases for similar proteins. Your homology model is built from the search results, comparing the model structure to the known template structure when building the model.

Applications of Homology Modeling

• Molecular interaction studies, such as molecular docking.
• Computer-aided drug discovery.
• Improving quantitative structure-activity relationship (QSAR) results.
• Overcoming phase problems in protein crystallography.

Creative BioMart is committed to providing a wide range of professional homology modeling services for various applications in the scientific field. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

Reference

1. Sliwoski G, Kothiwale S, Meiler J, et al.. (2014) Computational methods in drug discovery[J]. Pharmacological reviews. 66(1): 334-395.

• De Novo Prediction Service
• Fold Recognition Service