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SummaryMost rotamer libraries are generated from subsets of the PDB and do not fully represent the conformational scope of protein side chains. Previous attempts to rectify this sparse coverage of conformational space have involved application of weighting and smoothing functions. We resolve these limitations by using physics-based molecular dynamics simulations to determine more accurate frequencies of rotameric states. This work forms part of our Dynameomics initiative and uses a set of 807 proteins selected to represent 97% of known autonomous protein folds, thereby eliminating the bias toward common topologies found within the PDB. Our Dynameomics derived rotamer libraries encompass 4.8 × 109 rotamers, sampled from at least 51,000 occurrences of each of 93,642 residues. Here, we provide a backbone-dependent rotamer library, based on secondary structure ϕ/ψ regions, and an update to our 2011 backbone-independent library that addresses the doubling of our dataset since its original publication.

The evaluation of mechanical prosthetic heart valves would be aided by a more satisfactory animal model. For acute assessment, a variety of animals have been used, but for chronic studies, only larger animals (pigs, calves, baboons) have been employed, creating an expensive model with laboratory management difficulties. Previously, the use of dogs for chronic evaluation has been unsatisfactory because of the frequent occurrence of early sepsis and valve-related thrombotic deaths. We have modified our existing acute dog protocol to produce a successful chronic model. Our model employs perioperative systemic antibiotics, short cardiopulmonary bypass period (range 35–60 min), a minimum of perioperative intravenous lines, postoperative anticoagulation therapy, and strict postoperative antiseptic technique for blood sampling. To evaluate this model, 11 consecutive mongrel dogs underwent mitral valve replacement with either a standard Dacron sewing skirt or a newly devised carbon-coated Teflon sewing skirt No. 23 mm Bjork-Shiley Convexo Concave (CC) prosthetic valve. Nine animals (82%) survived and were evaluated after a predetermined observation interval of either 3 or 6 months for valve function, pannus formation, and possible carbon particle migration. At sacrifice, all animals had good hemodynamics and valve function, minimal pannus formation and no carbon washout. Consequently, this model provides a relatively inexpensive, reproducible method of chronic in vivo evaluation of prosthetic valve modifications.

The effect upon pancreatic blood flow of systemic hypoxia and hypercapnia was examined in 15 anesthetized puppies. Blood flow was measured by the 86 RbCl distribution technique. Reduction in arterial P O 2 and elevation of arterial P CO 2 were each found to effect significant mean reductions in pancreatic blood flow of 47 and 50%, respectively. Simultaneous measurements of duodenal blood flow showed no change from control levels.

To better determine the risks of transcatheter closure of a patent ductus arteriosus (PDA), a model of PDA was made in newborn piglets by using 5- to 7-mm angioplasty catheters to dilate the probe PDA. This maneuver resulted in a permanent PDA in most piglets. Four to 6 weeks later PDA closure was attempted using the Rashkind PDA occluder. Twelve such procedures were attempted, using clean but nonsterile technique. Nine of 12 PDAs were successfully closed. Two failures were the result of inability to successfully traverse the PDA. This problem was solved by using a long sheath to position the device properly. Four complications occurred, all related to device release: left pulmonary artery embolization in 1 case, femoral artery embolization in 1, torn pulmonic valve cusp in 1 and lodgment of a prosthesis on a pulmonic valve cusp. Two successfully implanted devices were infected at necropsy. This study demonstrates the value of a piglet model in testing transcatheter PDA occlusion devices, the importance of sterile technique in such procedures, the hazards of device retrieval through the right heart and the feasibility of transcatheter PDA closure.