Prediction of multiple conformational states of membrane proteins

Abstract: Predicting protein structures has long been an area of active research in the field ofbioinformatics. Great strides have recently been made in this area by googles DeepMindteam. They developed an AI called AlphaFold which is able to make the most accuratepredictions of protein structures as of date. With the advent of AlphaFold some considerthe problem solved. There is however an area in protein prediction that has lagged be-hind, that of multi conformational prediction. There are proteins that can take on oneout of several active forms in the body. Making predictions for these are harder than forsingle conformational proteins due to an increase in complexity and a lack of data. Apromising solution to this problem is to introduce noise to the input data AlphaFold usesto create a wider range of predictions. In this thesis multi conformational prediction withdifferent methods to introduce noise is evaluated. Dropout, disclosing templates, untar-geted Multiple sequence alignment(MSA) subsampling and targeted MSA subsamplingwere used. It was concluded introducing noise did indeed improve the prediction of mul-tiple conformations. Among them, MSA subsampling seemed to be the most effective,especially untargeted MSA subsampling. Dropout also seemed to slightly improve theresults while excluding template information did little to nothing. AlphaFold was unableto predict both structures for 6 out of 16 structures, even with introduced noise. No clearreason for why this could be determined, but the leading hypothesis is that AlhpaFoldwas unable to extract sufficient information about both conformations from the MSAdata for these proteins.