Modelling by homology of the HSV1-TK sequence embedded structural alignment

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Homology modeling is crucial for rational drug design when target protein 3D structures are unknown.
• This method relies on comparing isofunctional proteins to infer structural information from amino acid sequences.
• It is particularly valuable for proteins with divergent sequences but conserved functions, implying similar active site structures.

Purpose of the Study:

• To develop a theoretical procedure for predicting protein structures using homology modeling.
• To establish a sequence alignment between viral thymidine kinases and adenylate kinases based on functional similarity.
• To utilize known adenylate kinase structures as templates for predicting thymidine kinase active sites.

Main Methods:

• Employing a pattern recognition approach.
• Utilizing additive secondary structure prediction.
• Analyzing surface probabilities derived from residue variability.

Main Results:

• Achieved sequence alignment between viral thymidine kinases and adenylate kinases.
• Demonstrated the feasibility of using additive properties for sequence comparison.
• Established adenylate kinases as suitable templates for 3D structure prediction of thymidine kinase active sites.

Conclusions:

• Homology modeling, based on sequence and structural patterns, is a viable strategy for predicting protein active sites.
• The study provides a framework for deriving 3D structural insights into viral thymidine kinases.
• This approach facilitates rational drug design by enabling the modeling of ligand-protein interactions.