Jennifer Atkins
University of Reading, UK
Cardiovascular disease (CVD) is an ever-growing burden both worldwide and in UK, and is one of the leading causes of death worldwide. Often, CVDs progress into heart failure, where the heart can no longer pump effectively. The progression of CVDs to heart failure has been linked with single-gene mutations, including MLP; a multi-function protein found within the cytosol and nucleus of myocytes. To investigate mutations within MLP, homology models including IntFOLD4 were utilized to ascertain the potential structure and relevance of individual mutations in terms of their side chains. A combination of online protein bioinformatics tools were then used to assess the impact of these mutations upon function. Classical molecular dynamics is then used to observe the stability and flexibility of the mutants versus the wild type. Using bioinformatic tools, it is possible to direct wet lab experiments, saving time and reagents. From this study, mutants can be categorized into structural or functional impact groups, thus determining whether a structural biology route, or cell culture based studies would be most telling in how the mutations cause heart failure. From this, therapeutic routes can be considered and tailored based upon the mutants�?? effect.
Email: j.atkins@pgr.reading.ac.uk
