Toward better refinement of comparative models: predicting loops in inexact environments

Achieving atomic-level accuracy in comparative protein models is limited by our ability to refine the initial, homolog-derived model closer to the native state. Despite considerable effort, progress in developing a generalized refinement method has been limited. In contrast, methods have been described that can accurately reconstruct loop conformations in native protein structures. We hypothesize that loop refinement in homology models is much more difficult than loop reconstruction in crystal structures, in part, because side-chain, backbone, and other structural inaccuracies surrounding the loop create a challenging sampling problem; the loop cannot be refined without simultaneously refining adjacent portions. In this work, we single out one sampling issue in an artificial but useful test set and examine how loop refinement accuracy is affected by errors in surrounding side-chains. In 80 high-resolution crystal structures, we first perturbed 6-12 residue loops away from the crystal conformation, and placed all protein side chains in non-native but low energy conformations. Even these relatively small perturbations in the surroundings made the loop prediction problem much more challenging. Using a previously published loop prediction method, median backbone (N-Calpha-C-O) RMSD's for groups of 6, 8, 10, and 12 residue loops are 0.3/0.6/0.4/0.6 A, respectively, on native structures and increase to 1.1/2.2/1.5/2.3 A on the perturbed cases. We then augmented our previous loop prediction method to simultaneously optimize the rotamer states of side chains surrounding the loop. Our results show that this augmented loop prediction method can recover the native state in many perturbed structures where the previous method failed; the median RMSD's for the 6, 8, 10, and 12 residue perturbed loops improve to 0.4/0.8/1.1/1.2 A. Finally, we highlight three comparative models from blind tests, in which our new method predicted loops closer to the native conformation than first modeled using the homolog template, a task generally understood to be difficult. Although many challenges remain in refining full comparative models to high accuracy, this work offers a methodical step toward that goal.     

Dynamics in rhinoplasty

Nasal dynamics were studied on 87 patients undergoing rhinoplasty of one zone or two distant nasal zones. Statistical analysis of the results revealed that reduction of the nasion area, besides setting the soft tissue back, gave the appearance of increased intercanthal distance and lengthened the nose. Reduction of the nasal bridge resulted in a wider appearance on frontal view and a cephalically rotated tip on profile. Augmentation of the bridge affected the nose reversely. Tip cephalad rotation was achieved by resecting one of the three areas: the cephalad portion of the lower lateral cartilages (affecting the rims more), the caudal septum (affecting the central portion more), and the caudal portion of the medial crura of the lower lateral cartilages (affecting the central portion only). Resection of the alar base not only narrowed the nostrils but also moved the alar rim caudally. Furthermore, it reduced tip projection when a large alar base reduction was done. Reduction of the nasal spine increased the upper lip length on profile and reduced tip projection when a large reduction took place. Significant reduction in caudal nose projection resulted in widening of the alar base.     

Cosmetic rhinoplasty

Rhinoplasty is safe, relatively painless and, if patients are carefully selected, quite successful. Psychological and personal benefits amply justify the procedure. Frequent indications are feelings of social rejection or ridicule and racial discrimination. Psychoneurotic patients with severe complexes, however, are poor subjects for rhinoplasty and should not be operated upon. It is doubtful that rhinoplasty grossly changes the physiologic integrity of the nose. Psychological trauma to the patient during hospitalization is to be avoided, sedation properly gauged for each patient, and complete block anesthesia used to preserve the cough reflex. The operation is brief and a small splint is worn for a few days. Complications are rare.     

Male rhinoplasty

Rhinoplasty is one of the most complex and challenging operations in plastic surgery. This complexity is increased among male patients, because male patients tend to have relatively nonspecific complaints, are typically more demanding, and are regarded as being much less attentive during consultations. It is critical for the surgeon to verify that the male patient has realistic goals before he undergoes an operation, and the surgeon must confirm that the male patient has heard and understood all of the risks, benefits, and options. It is essential that masculine features be preserved for male rhinoplasty patients. Excessive dorsal reduction or tip refinement produces unsatisfactory results. A comprehensive discussion of proper evaluation of the male nose, surgical planning, intraoperative techniques, and postoperative treatment is presented. These tools should allow plastic surgeons to produce a balanced harmonious nose in relation to the rest of the face.     

On rhinomanometry in rhinoplasty

Changes in nasal obstruction, nasal airway resistance, and postoperative nose appearance were evaluated in 92 rhinoplasty patients. Fifty-six patients had a deviation of their nose from the midline preoperatively. They were improved according to rhinomanometry whether the rhinoplasty was combined with a functional septoplasty or with a submucous resection. Among the other 36 patients who did not have a deviation of the nose from the midline, 23 had a rhinoplasty combined with a functional septoplasty and 13 had no surgery on the septum at all. Rhinomanometrically, only patients operated on with the combined operation were improved; the rest became worse, even in terms of nasal obstruction. Among 58 patients from both groups with preoperative nasal obstruction, there was agreement for 76 percent between the subjective and rhinomanometric changes. The advantages of giving the rhinomanometric results in a polar coordinate system are discussed.     

Dynamics of rhinoplasty

Nasal dynamics were studied on 87 patients undergoing rhinoplasty of one zone or two distant nasal zones. Statistical analysis of the result revealed that reduction of the nasion area, besides setting the soft tissue back, gave the appearance of increased intercanthal distance and lengthened the nose. Reduction of the nasal bridge resulted in a wider appearance on front view and a cephalically rotated tip on profile. Augmentation of the bridge affected the nose reversely. Tip cephalad rotation was achieved by resecting one of the three areas: the cephalad portion of the lower lateral cartilages (affecting the rims more), the caudal septum (affecting the central portion more), and the caudal portion of the medial crura of the lower lateral cartilages (affecting the central portion only). Resection of the alar base not only narrowed the nostrils but also moved the alar rim caudally. Furthermore, it reduced tip projection when a large alar base reduction was done. Reduction of the nasal spine increased the upper lip length on profile and reduced tip projection when a large reduction took place. Significant reduction in caudal nose projection resulted in widening of the alar base.     

Secondary rhinoplasty.

Secondary rhinoplasty is a highly complex, judgmental type of surgery. It is only through analysis of the successful treatment of various problems in secondary rhinoplasty that meaningful information can be obtained.     

Temporoparietal free fascia grafts in rhinoplasty

The temporoparietal fascial graft provides adequate coverage, contour, and bulk on the cartilage dorsum of the nose, as well as an inconspicuous donor site. In my opinion, this technique not only prevents the occurrence of noticeable sharp edges of the cartilage graft, but also adds to the smooth contour of the reconstructed nasal dorsum. The improved results either in primary and secondary rhinoplasty would seem to justify this technique. Some variations in fascia grafts are presented with clinical examples.