Screening for Common Antimicrobial Sequence Motifs and Testing Their Activity Against Model of the Inner Membrane of Escherichia coli
Author
Hitov, Svetomir Todorov
Term
4. term
Education
Publication year
2017
Submitted on
2017-06-10
Pages
67
Abstract
Antimikrobielle peptider (AMP’er) er kortere proteinfragmenter med potentiale som alternativer til traditionelle antibiotika og kan i nogle tilfælde være indlejret i større proteiner og frigives ved kløvning. Dette projekt undersøger, om fælles sekvensmotiver i kendte, membranaktive AMP’er kan identificeres og bruges til at finde nye, endnu ikke annoterede kandidatpeptider, og hvordan sådanne peptider påvirker en model af Escherichia colis indre membran. Arbejdet opstiller en pipeline, der omfatter: indsamling af annoterede AMP-sekvenser fra databaser, motivopdagelse og opbygning af søgeprofiler, søgning i UniRef-klynger for beslægtede motiver (herunder i længere forløberproteiner), og molekylærdynamik-simuleringer for at analysere peptid–membran-interaktioner. Der anvendes både grovkornede (MARTINI) og atomistiske simuleringer, med analyser af membrantykkelse, areal pr. lipid og kontaktmønstre mellem peptid og lipider. Introduktionen gennemgår centrale virkemekanismer (fx barrel-stave-, toroidal-pore- og carpet-modeller) og fremhæver cecropiner som en relevant peptidfamilie. Konkrete resultater af motivscreeningen, de fundne UniRef-kandidater og simulationsstudierne fremgår ikke af dette uddrag, men præsenteres senere i afhandlingen.
Antimicrobial peptides (AMPs) are short protein fragments with potential as alternatives to conventional antibiotics and, in some cases, are embedded in larger proteins and released by proteolytic cleavage. This thesis asks whether common sequence motifs in known, membrane-active AMPs can be identified and used to discover new, unannotated candidate peptides, and how such peptides affect a model of the Escherichia coli inner membrane. It outlines a pipeline that includes collecting annotated AMP sequences from databases, discovering recurrent motifs and building search profiles, scanning UniRef clusters for related motifs (including within longer precursor proteins), and using molecular dynamics simulations to probe peptide–membrane interactions. Both coarse-grained (MARTINI) and all-atom simulations are employed, with analyses of membrane thickness, area per lipid, and peptide–lipid contact patterns. The introduction reviews key mechanisms of action (e.g., barrel-stave, toroidal-pore, and carpet models) and highlights cecropins as a relevant peptide family. Specific outcomes of the motif screen, identified UniRef candidates, and the simulation results are not included in this excerpt but are presented later in the thesis.
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