Analysis of the ligand transport pathway through a eukaryotic transporter using Caver Web server

سال انتشار: 1399
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 360

نسخه کامل این مقاله ارائه نشده است و در دسترس نمی باشد

استخراج به نرم افزارهای پژوهشی:

لینک ثابت به این مقاله:

شناسه ملی سند علمی:

ICIBS01_102

تاریخ نمایه سازی: 2 آذر 1399

چکیده مقاله:

Introduction & Objective: Protein tunnels and channels are key transport pathways that allow ligands to pass between proteins' external and internal environments. These tunnels are attractive targets for drug design. An important challenge we encounter is how ligands access to their binding site in the corresponding channels. Caver Web is an interactive web server suitable for comprehensive analysis of protein tunnels/channels as well as the ligands’ transport. In this study, we used Caver Web to detect and characterization of the channels within the cationic amino acid transporter 1 (CAT-1) and analyzed the transport of a series of hit compounds through the main channel.Materials & Methods: CAVER Web version 1.0 was used to calculate the tunnels and channels in the protein structure of the CAT-1 which was previously modeled using MODELLER 9.20 software and equilibrated in membrane system using GROMACS package for 1 μs. Subsequently, the 15 top hit compounds selected based on the docking energy were subjected to analysis through the identified channel.Results: About 32 tunnels and channels were identified within the cationic amino acid transporter 1. The energy profiles and trajectories for the passage of the ligands through the main channel were calculated. We found out that the compound with Drug Bank ID 07102 and Zinc ID 40916505 have the easiest access to the binding site of the main channel.Conclusion: Considering the findings obtained here, it can be concluded that the binding strength of the ligands to the binding sites is not enough criterion in the drug discovery projects. But, the easiness of access to the druggable site for the hit compounds has significance equal with binding free energy to the binding site.

کلیدواژه ها:

نویسندگان

Parinaz Parsi

Bioinformatics Lab., Department of Biology, Razi University, Kermanshah, Iran

Hamid Mahdiuni

Bioinformatics Lab., Department of Biology, Razi University, Kermanshah, Iran