Bioprospecció computacional de timidina quinases (TK) modernes i ancestrals depenents del profàrmac Ganciclovir

Abstract

The overall objective of this work is to obtain enzymes that are able to accept prodrug through

computational bioprospecting techniques. To achieve this goal, homologous sequences from the HSV-TK

and EHV4-TK enzyme sequences will be screened, processed and a multiple sequence alignment will be

performed. Subsequently, the generation of three-dimensional structural models to analyse the variants. And

finally, a molecular docking study to verify the enzyme-linker affinity. This approach will allow us to

evaluate the affinity of the different candidates. Therefore, once the objective of this work has been achieved,

we will have contributed to the identification of possible alternative enzymes in enzyme-propharmaceutical

systems, thus contributing to the development of efficient therapies.

No less important, another objective of this work is to become familiar with the computational techniques

and methodologies used in the field of structural biology and enzyme design. The application of techniques

such as homology search, multiple sequence alignment, three-dimensional modelling using AlphaFold and

the analysis of enzyme-ligand interactions using molecular docking represents a very important training

opportunity