Bioinformatics Research: Protein Folding, Docking and Prediction of Biological Activity

Number: NSF I02/16, 12.12.14
Title: Bioinformatics Research:  Protein Folding, Docking and Prediction of Biological Activity
Basic Organization: South-West University “Neofit Rilski”  – Blagoevgrad
Funding:  National Science Fund -Ministry of Education and Science
Project Manager: Assoc. Prof. PhD Ivan Trenchev

Aims of the project

   By performing in silico (computerized) experiments we aim:

  • modeling and optimizing of the structure of mu-, delta- and kappa- opioid receptors, cannabinoid receptors and neurotensin receptors;
  • determining the structure of the ligand-receptor complex and the minimum free energy of binding in certain structures of receptor and ligand, and studing the method of connection in order to offer modifications to ligands;
  • prediction of biological activity;
  • development of a mathematical model for predicting the biological activity by using the results of molecular docking of new ligands and the results of in vitro tests;
  • studying the applicability of cloud structures and server virtualization tasks in protein folding, docking and the prediction of biological activity;

  Methods and models to achieve the objectives:

  • “hydrophobic-hydrophilic” model;
  • method of homology modeling;
  • solving the problem of protein folding by using the following three types of combinatorial algorithms: heuristic, combinatorial-optimizational, and approximational;
  • determining the binding mode of the ligand and the receptor using geometrical and energetic methods;
  • application of ligand-based and structure-based approaches, in which: molecular analysis of the fields of protein homology modeling, docking and virtual screening of bioactive compounds, the determination and analysis of protein-ligand interactions for the 3d structure of the target biomacromolecule.

Key results:

  • modeling and optimization of the 3d structure of the study receptors – opioid, cannabinoid, and neurotensin;
  • development of a mathematical model describing the relationship between the parameters and the results of the docking of particular biological importance of in vitro assays to predict biological activity of the compounds.
  • determination of the quantitative relationship between the biological activity of a series of compounds and their physico-chemical properties.

Stages

First stage

  • Installing the necessary software packages and operating systems.
  • Modeling and optimizing the structure of mu-, delta-and kappa-opioid, neurotensin and cannabinoid receptors.
  • Determining the structure of the ligand-receptor complex and the minimum free energy of binding at the known structures of the receptor and the ligand
  • Create virtual modules for scientific tasks provided by the project.
  • Study the applicability of cloud structures and server virtualization tasks in protein folding, docking and determination of biological activity.
  • Study the binding mode of the ligand to the receptor in order to propose modifications to the ligands.
  • Creating a web portal with the possibility of publishing the results of the project.

Second stage

  • Molecular Docking of mu-, delta-and kappa-opioid receptors with selected ligands.
  • Molecular docking of neurotensin receptors with selected ligands.
  • Molecular docking of cannabinoid receptors with selected ligands.
  • Development of a mathematical model for predicting the biological activity using the results of the molecular docking of new ligands.
  • Determination of biological activity of the mu-, delta-and kappa-opioid, neurotensin and cannabinoid receptors.
  • Organizing webinars.
  • Creating an interactive platform where results and expertise of the members of the project will be promoted.

Participants

Name Organization
Assoc. Prof. PhD Ivan Trenchev SWU-Blagoevgrad
Prof. Nevena Pencheva SWU-Blagoevgrad
Assist. Anton Stoilov SWU-Blagoevgrad
Assist.  Radoslav Mavrevski SWU-Blagoevgrad
Assist. Ivan Todorin SWU-Blagoevgrad
Prof. Nicola Yanev IMI-BAS
Assist. Tatyana Dzimbova IMB-BAS
Fatima Sapundzhi, PhD studnet SWU-Blagoevgrad
Metodi Traykov, PhD studnet SWU-Blagoevgrad
Gergana Koroleova, PhD studnet SWU-Blagoevgrad

Specific actions of SWU “Neofit Rilski” include the provision of facilities of the center for advanced bioinformatics studies (TSSBI) for the project. Facilities of TSSBI includes seminar hall with 12 work places, computer equipment, server room equipped with 5 high computational power servers. SWU “West University” will support this project by incurring overhead costs – electricity, water, etc. TSSBI will provide high-speed connectivity to the Internet and access to the infrastructure of the university.

In addition SWU “Neofit Rilski” will:

  • supplies software packages Matlab, GOLD and Hyperchem, purchased from SWU “West University”;
  • promote the use of seminar halls, hall for conferences at SWU “Neofit Rilski” and the necessary chemical laboratories;
  • provide a building – University Center “Bachinovo” to conduct short-term project events;
  • if necessary for the execution of the project SWU “Neofit Rilski” will contribute to access GRID systems of other institutions;
  • assist in the distribution and promotion of project results based on contracts for cooperation with universities in Greece, France, Germany, Italy, Macedonia, Albania, etc.;
  • information support (access to electronic library database, interlibrary loan, document delivery electronically);
  • providing administrative, technical and financial assistance in the administration of the project;
  • support the work of PhD students – opportunities to participate in conferences organized by SWU and publication in scientific journals issued by the university;
  • all unmentioned activities that would contribute to the successful outcome of the project.