Faculty Bibliography

Rosetta ab initio protein structure predictions in CASP4 were considerably more consistent and more accurate than previous ab initio structure predictions. Large segments were correctly predicted (>50 residues superimposed within an RMSD of 6.5 A) for 16 of the 21 domains under 300 residues for which models were submitted. Models with the global fold largely correct were produced for several targets with new folds, and for several difficult fold recognition targets, the Rosetta models were more accurate than those produced with traditional fold recognition models. These promising results suggest that Rosetta may soon be able to contribute to the interpretation of genome sequence information.

To generate structures consistent with both the local and nonlocal interactions responsible for protein stability, 3 and 9 residue fragments of known structures with local sequences similar to the target sequence were assembled into complete tertiary structures using a Monte Carlo simulated annealing procedure (Simons et al., J Mol Biol 1997; 268:209-225). The scoring function used in the simulated annealing procedure consists of sequence-dependent terms representing hydrophobic burial and specific pair interactions such as electrostatics and disulfide bonding and sequence-independent terms representing hard sphere packing, alpha-helix and beta-strand packing, and the collection of beta-strands in beta-sheets (Simons et al., Proteins 1999;34:82-95). For each of 21 small, ab initio targets, 1,200 final structures were constructed, each the result of 100,000 attempted fragment substitutions. The five structures submitted for the CASP III experiment were chosen from the approximately 25 structures with the lowest scores in the broadest minima (assessed through the number of structural neighbors; Shortle et al., Proc Natl Acad Sci USA 1998;95:1158-1162). The results were encouraging: highlights of the predictions include a 99-residue segment for MarA with an rmsd of 6.4 A to the native structure, a 95-residue (full length) prediction for the EH2 domain of EPS15 with an rmsd of 6.0 A, a 75-residue segment of DNAB helicase with an rmsd of 4.7 A, and a 67-residue segment of ribosomal protein L30 with an rmsd of 3.8 A. These results suggest that ab initio methods may soon become useful for low-resolution structure prediction for proteins that lack a close homologue of known structure.

The bowed lower eyelid, with scleral show, is a common but untoward result following blepharoplasty with even minimal skin excision. A number of conditions, unrecognized preoperatively, can predispose a patient to scleral show. These include eyelid laxity with or without atrophic orbicularis muscle tone, lax canthal tendons, hypoplastic malar eminences, unrecognized Graves' ophthalmopathy, unilateral high myopia, or the secondary blepharoplasty. Suspension of the tarsus of the lower eyelid, concomitant with or following blepharoplasty, can straighten bowed lids and provide 2 to 3 mm of elevation, if desired. A classification of patients likely to develop scleral show is presented along with a revised technique of tarsal suspension

Paralytic ectropion can be corrected with numerous procedures. Advocates of particular procedures have previously been unable to quote statistical rates of success for each procedure over significant lengths of time. This study reviews over 200 cases of paralytic ectropion, representing the spectrum of seventh nerve disease seen at an eye and ear specialty hospital and a general medical facility. Of all eyelid implantation devices 93 to 95% failed to work or needed reoperation by 3 years postoperatively. Soft tissue surgery without prosthetic implants or exoplants provided 60% success after a 3-year follow-up. Eyelid elevation or tightening coupled with surgery for facial reanimation produced a higher rate of success at 3 years (83%). An overwhelming number of patients (62%) complained of some degree of epiphora after any or all procedures. Based on these findings, soft tissue surgery without prosthetic implants or exoplants has a higher rate of success