Homology Modeling of P-glycoprotein for Detecting Remote Protein Homologies

摘要

Proteins are polymers of amino acids and an important class of biological macromolecules present in all organisms. P-glycoprotein (P-gp) is one of the xenobiotic transport proteins implicated in multidrug resistance in neoplastic tissues. It is a cell membrane-associated protein that transports a variety of drug substrates. It is present in organ systems that influence drug absorption (intestine), distribution to site of action (central nervous system and leukocytes), and elimination (liver and kidney), as well as several other tissues. In cancer tissue with high expression of this protein, P-gp functions as a drug export pump that decreases intracellular concentrations of numerous chemotherapeutic agents. P-gp (ABCB1) appears to have developed as a mechanism to protect the body from harmful substances. Drug resistance is the major constraint for chemotherapeutic agents used for the treatment of neoplastic diseases. The prediction of proper protein sequence and structure of protein help in many ways to medical science and in the field of bio-computing. The modelling technique is used for detecting remote protein homologies, hi this paper, P-gp has been taken as the target sequence. The protein has been processed under molecular modelling. The creation of mathematical models of molecular properties and behaviour is modelling. To know the proper molecular model of the protein, the target sequence was matched with protein structure database to find the templates. The model has been designed using the modeller which is the homology modelling process. The target sequence has been matched with protein structure database with the help of BLAST. The maximum identity accession has been found and the structure was analyzed. The target sequence acted as a query and aligned with template structure. This protein modelling and structure designs are important for structure drug design, to minimize the time complexity and also to make the clinical trial process easier.