This project is part of a collaboration funded by a STINT grant. At Umeå University the Ramstedt group performs experimental studies, which are complemented with computer simulations performed in the group of Thereza Soares at University of Pernambuco, Brazil. The main goal of the present international cooperation grant is to understand the biocompatibility of biomaterials towards bacterial and mammalian cells.
Computer time allocation is sought to perform atomistic simulations of bacterial outer membranes and engineered antibacterial surfaces. Previously, we have developed atomistic models of the rough LPS and Lipid-A membranes, which have been validated via MD simulations along time scales varying between 300 nanoseconds to 1 microseconds. These models have been further expanded to include chemical variants of the lipopolysaccharide (LPS) molecule, the major constituent of the outer membrane. Chemical variants or chemotypes impart distinct physical-chemical properties to the outer membrane surface with important implications for bacterial adhesion and resistance of different strains. The development of the LPS variants or chemotypes was possible due to computer allocation of SNIC at High Performance Computing Center North (HPC2N). The SNIC allocation lead to the publication of 04 manuscripts (below). As continuance of the project we will validate molecular models for polymers brushes developed to be compatible with the atomistic model of the LPS membranes. Polymer brushes are a class of polymers formed by ordered tethering of polymeric chains to a surface. Molecular brushes will exhibit reversible conformational changes in response to external stimuli, which can be limited to the single molecule and easily observed by atomic force microscopy. The chemical and mechanical robustness of polymer brushes has enabled the development of functional surface coatings with enhanced long-term stability. These polymers are also highly amenable to chemical modifications for diverse applications for example inclusion of antimicrobial peptides. Selected polymers as well as peptides are experimentally under investigation by our team and collaborators with the goal to optimize functionalities that repel bacterial adhesion while minimizing damage to mammalian cells. Molecular dynamics simulations will be performed for pMETAC, polysulphonate, pDMAEMA and pMEDSAH polymer chains from the atomistic models developed using the previous computer allocation (SNIC 2015/1-129, 2016/1-491). These models have been developed to be compatible with our previously developed LPS parameters. Currently, we have atomic parameters and topologies for all four polymers so that the characterization of the structure and conformational dynamics of polymer brushes can be undertaken. Computational simulations based on an atomistic representation of molecular brushes have been performed by several groups. However, there are no atomic parameters or previous simulations for the polymer brushes we are currently investigating.
Nascimento, Pontes, Lins, Soares, Chem Commun (Camb) 2014, 50, 231-233; Dias, da Hora, Ramstedt, Soares, Chem. Theory Comput. 2014, 10, 2488-2497; Dias, Li, Soares, Alexov, J. Comput. Chem. 2014, 35, 1418-1429; Santos,Pol-Fachin, Lins, Soares, J. Chem. Inf. Model. 2017, 57, 2181-2193