Comparison of Rosetta flexible-backbone computational protein design methods on binding interactions

ABSTRACTComputational design of binding sites in proteins remains difficult, in part due to limitations in our current ability to sample backbone conformations that enable precise and accurate geometric positioning of side chains during sequence design. Here we present a benchmark framework for comparison between flexible-backbone design methods applied to binding interactions. We quantify the ability of different flexible backbone design methods in the widely used protein design software Rosetta to recapitulate observed protein sequence profiles assumed to represent functional protein/protein and protein/small molecule binding interactions. The CoupledMoves method, which combines backbone flexibility and sequence exploration into a single acceptance step during the sampling trajectory, better recapitulates observed sequence profiles than the BackrubEnsemble and FastDesign methods, which separate backbone flexibility and sequence design into separate acceptance steps during the sampling trajectory. Flexible-backbone design with the CoupledMoves method is a powerful strategy for reducing sequence space to generate targeted libraries for experimental screening and selection.

Modular Motion-Structure Design Model for Planetary Surface Sampling

Because there are less restrictions in space, a variety of different movement patterns and equipment structures may be used during the process of planetary surface sampling. Traditionally, the optimal analysis for surface sampling is focused on specific equipment structures and movements; in contrast, a new modular motion-structure design model for surface sampling, which is a more flexible model, is discussed in this paper. By establishing and combining two basic module groups, namely, the motion group and the structure group, this new design model can define and analyse multiple movement patterns and structures. For the motion group, calculating the sampling trajectory is the main purpose, in which there are two basic modules: tridimensional uniform rectilinear movements and tridimensional uniform circular movements. The two basic motion modules can be freely combined in a given coordinate system to simulate a random sampling trajectory. The structure group contains a series of curved and flat plates, which can be defined by a set of unified parameters (including section, extension, and cutting parameters). By assigning different values to these parameters, the curved or flat plates can represent different external shapes. The different structures of the various pieces of surface sampling equipment can be simulated by combining these different plates. In addition to defining these basic modules, analysing the coupling among different modules, which can be simplified to the relationship between velocity and surface, plays an important role in establishing this design model. Based on the modular design theory, this new model will not only reduce the difficulty of analysis but also improve accuracy for planetary surface sampling.