Protein modelling by the zipping and assembly method with limited NMR-derived constraints

Licentiate thesis, 2017

Molecular dynamics simulations, often combined with simulated annealing, are commonly used when calculating structural models of proteins, e.g. based on NMR experiments. However, one is often faced with limited and, sometimes, insufficient information for determining a well-resolved 3D structure. In addition, the type of data available for different proteins may vary: ranges for torsion angles, distance ap- proximations, relative orientation of different molecular parts etc. We are using whatever structural information is around, together with a dynamic programming approach (Zipping and Assembly) for searching the space of feasible conformations to rapidly determine 3D structures that are consistent with the input constraints. Time-efficiency is im- portant for good sampling of the conformational space and necessary to replace expensive, complex and time consuming experiments. Our approach benefits from having both high level and low level descriptions of conformational features and constraints and the possibility to infer new constraints from those that are given.