Vaccine research: Molecular simulation for the assessment of structural requirements in complement-mediated bactericidal events.

Abstract

The BacAbs-MS project encompasses the molecular-simulation part of a larger project entitled "Assessment of structural requirements in complement-mediated bactericidal events: Towards a global approach to the selection of new vaccine candidates" (BacAbs), a STREP under FP6-2005-LIFESCIHEALTH-7. The BacAbs project proposes the evaluation, through a novel multidisciplinary approach, of the structural requirements for viable bactericidal vaccine candidates as well as the development of bioinformatics tools to predict compliance with such structural requirements. To this end, a systematic analysis of sequence, structure, dynamics and interactions of potential antigens will be undertaken using as model system serogroup-B Neisseria meningitidis, a pathogen causing septicemia and meningitis and for which no effective vaccine exists. This analysis involves the application of several computational techniques, some of which posing extreme demands on CPU time, to the study of complex biomolecular systems. Specifically, a list of antigens (proteins) and their complexes with antibodies and the complement component C1q will be studied using: i) Monte-Carlo simulations of coarse-grained protein models to assist structure determination by experimental partners in the BacAbs consortium, ii) extensive molecular-dynamics simulations to characterize the conformational properties of specific protein regions (epitopes) and, iii) protein-protein docking using a combination of algorithms. This work can only be performed for a significant number of proteins and protein complexes if supercomputing resources are available.