138 research outputs found
RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite
Macromolecular modeling and design are increasingly useful in basic research, biotechnology, and teaching. However, the absence of a user-friendly modeling framework that provides access to a wide range of modeling capabilities is hampering the wider adoption of computational methods by non-experts. RosettaScripts is an XML-like language for specifying modeling tasks in the Rosetta framework. RosettaScripts provides access to protocol-level functionalities, such as rigid-body docking and sequence redesign, and allows fast testing and deployment of complex protocols without need for modifying or recompiling the underlying C++ code. We illustrate these capabilities with RosettaScripts protocols for the stabilization of proteins, the generation of computationally constrained libraries for experimental selection of higher-affinity binding proteins, loop remodeling, small-molecule ligand docking, design of ligand-binding proteins, and specificity redesign in DNA-binding proteins
Protein Design Using Continuous Rotamers
Optimizing amino acid conformation and identity is a central problem in computational protein design. Protein design algorithms must allow realistic protein flexibility to occur during this optimization, or they may fail to find the best sequence with the lowest energy. Most design algorithms implement side-chain flexibility by allowing the side chains to move between a small set of discrete, low-energy states, which we call rigid rotamers. In this work we show that allowing continuous side-chain flexibility (which we call continuous rotamers) greatly improves protein flexibility modeling. We present a large-scale study that compares the sequences and best energy conformations in 69 protein-core redesigns using a rigid-rotamer model versus a continuous-rotamer model. We show that in nearly all of our redesigns the sequence found by the continuous-rotamer model is different and has a lower energy than the one found by the rigid-rotamer model. Moreover, the sequences found by the continuous-rotamer model are more similar to the native sequences. We then show that the seemingly easy solution of sampling more rigid rotamers within the continuous region is not a practical alternative to a continuous-rotamer model: at computationally feasible resolutions, using more rigid rotamers was never better than a continuous-rotamer model and almost always resulted in higher energies. Finally, we present a new protein design algorithm based on the dead-end elimination (DEE) algorithm, which we call iMinDEE, that makes the use of continuous rotamers feasible in larger systems. iMinDEE guarantees finding the optimal answer while pruning the search space with close to the same efficiency of DEE. Availability: Software is available under the Lesser GNU Public License v3. Contact the authors for source code
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Growth Mindset Predicts Cognitive Gains in an Older Adult Multi-Skill Learning Intervention
Growth mindset (belief in the malleability of intelligence) is a unique predictor of young learners' increased motivation and learning, and may have broader implications for cognitive functioning. Its role in learning in older adulthood is unclear. As part of a larger longitudinal study, we examined growth mindset and cognitive functioning in older adults engaged in a 3-month multi-skill learning intervention that included growth mindset discussions. Before, during, and after the intervention, participants reported on their growth mindset beliefs and completed a cognitive battery. Study 1 indicated that intervention participants, but not control participants, increased their growth mindset during the intervention. Study 2 replicated these results and found that older adults with higher preexisting growth mindsets showed larger cognitive gains at posttest compared to those with lower preexisting growth mindsets. Our findings highlight the potential role of growth mindset in supporting positive learning cycles for cognitive gains in older adulthood
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