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Research areas
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computer simulations of proteins, membranes, and their interactions
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development and application of models ranging from all-atom to highly coarse-grained
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Molecular Dynamics, Monte Carlo, free energy calculations, Hamiltonian Replica Exchange, enhanced sampling
Main objectives
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investigation of the proteins sensitivity to the membrane composition and shape - cell organization, protein activation and targeting
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protein self-assembly - amyloid fibrils and virus capsids
Content of research
Our aim is to elucidate the key protein-membrane and protein-protein interactions that regulate cellular signaling, transport, and are the important part of our immune system. Change in these interactions can result in lethal diseases ranging from cancer to Alzheimer’s disease. In particular, we develop and apply multi-scale computer simulations (from highly coarse-grained to all-atom level) and theory to determine the relation between protein sequence and their assembly or preferred membrane composition and morphology, e.g. the aggregation of amyloid peptides enhanced or retarded by specific lipids. Such molecular information can be used to understand protein localization in cells, evaluate the risk of the diseases, develop new therapeutic peptides (antimicrobial peptides, sensors, target specific drug carriers), and suggest new treatment strategies (including lipid diet and altering lipid metabolism).
1. Influence of membrane properties on peptide conformations
Supervisor: doc. RNDr. Robert Vácha, PhD.
Annotation
Peptide and protein conformations are influenced by composition of phospholipid membrane, which they are interacting with. This is particularly important for antimicrobial and neurodegenerative peptides (such as Abeta peptide related to Alzheimer’s disease), which can disrupt cellular membrane by formation of toxic membrane pores. The lipid composition of the membrane can enhance or prevent the peptide aggregation and/or pore formation and thus determine the fate of the cell. Despite the importance, we do not understand the relation except few recent examples (e.g. DOI: 10.1002/anie.201603178). The aim of this project is to unravel the relationship between the membrane composition and peptide conformations. This information could lead to a new diet preventing the Alzheimer’s disease or to a rational design of new antimicrobial peptides. Student will master tools of computer simulations, in particular molecular dynamics technique, and methods to calculate free energies. Moreover, he/she will learn advantages and disadvantages of various protein and membrane parameterizations including all-atom and coarse-grained models.
Keywords: protein conformations, phospholipid membrane, neurodegenerative peptides, Alzheimer’s disease, Abeta peptide, peptide conformations, membrane parameterizations
2. Protein sensitivity of membrane curvature
Supervisor: doc. RNDr. Robert Vácha, PhD.
Annotation
The control of biological membrane shape and composition is vital to eukaryotic life. The shape is so specific that it allows us to recognize various organelles in the cell. Despite a continuous exchange of material, organelles maintain a precise combination and organization of membrane lipids, which is crucial for their function and the recruitment of many peripheral proteins. Membrane shape thus enables the cell to organize proteins and their functions in space and time, without which serious diseases can occur. Moreover, membrane curvature and lipid content can be specific to cancer cells, bacteria, and enveloped virus coatings, which could be utilized for selective targeting. The aim of this project is to unravel the relationship between the protein sequence and the preferred membrane. This will lay the foundations for the design of new protein motifs sensitive to membranes with a specific curvature and composition on enveloped viruses, organelles and cells. Student will master tools of computer simulations, in particular molecular dynamics technique, and methods to calculate free energies. Moreover, he/she will learn advantages and disadvantages of various protein and membrane parameterizations including all-atom and coarse-grained models.
Keywords: membrane curvature, protein sequencing, protein motifs design, membrane parameterizations
