Generalized biomolecular modeling and design with RoseTTAFold All-Atom.

Deep-learning methods have revolutionized protein structure prediction and design but are presently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA), which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies that contain proteins, nucleic acids, small molecules, metals, and covalent modifications, given their sequences and chemical structures. By fine-tuning on denoising tasks, we developed RFdiffusion All-Atom (RFdiffusionAA), which builds protein structures around small molecules.

Accurate prediction of protein-nucleic acid complexes using RoseTTAFoldNA.

Protein-RNA and protein-DNA complexes play critical roles in biology. Despite considerable recent advances in protein structure prediction, the prediction of the structures of protein-nucleic acid complexes without homology to known complexes is a largely unsolved problem. Here we extend the RoseTTAFold machine learning protein-structure-prediction approach to additionally predict nucleic acid and protein-nucleic acid complexes.

Computational design of sequence-specific DNA-binding proteins.

Sequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize specific target sequences through interactions with bases in the major groove, and employ this method in conjunction with experimental screening to generate binders for 5 distinct DNA targets.

Model of anesthesia care that combines anesthesiologists and registered nurses during cataract surgery.

Purpose: To determine the safety and practicality of a combined anesthesiologist and registered nurse model of anesthesia care in cataract surgery.

Setting: Mayo Clinic, Rochester, Minnesota, USA.

Design: Case series.

Clostridial sacroiliitis in a patient with fecal incontinence: a case report and review of the literature.

Introduction: Image-guided sacroiliac joint injections are frequently employed for both diagnostic and therapeutic relief of low back pain.

Case Report: An 83-year-old male with chronic lumbrosacral pain previously responsive to right sacroliac joint injections presented for repeat injection. His medical history included Parkinsonism and stool incontinence.