Identifying Conformational Isomers of Organic Molecules in Solution via Unsupervised Clustering.

We present a systematic approach for the identification of statistically relevant conformational macrostates of organic molecules from molecular dynamics trajectories. The approach applies to molecules characterized by an arbitrary number of torsional degrees of freedom and enables the transferability of the macrostates definition across different environments. We formulate a dissimilarity measure between molecular configurations that incorporates information on the characteristic energetic cost associated with transitions along all relevant torsional degrees of freedom. Such metric is employed to perform unsupervised clustering of molecular configurations based on the Fast Search and Find of Density Peaks algorithm. We apply this method to investigate the equilibrium conformational ensemble of Sildenafil, a conformationally complex pharmaceutical compound, in different environments including the crystal bulk, the gas phase, and three different solvents (acetonitrile, 1-butanol, and toluene). We demonstrate that while Sildenafil can adopt more than 100 metastable conformational configurations, only 12 are significantly populated across all of the environments investigated. Despite the complexity of the conformational space, we find that the most abundant conformers in solution are the closest to the conformers found in the most common Sildenafil crystal phase.

Outcomes after the Stainsby procedure in the lesser toes: an alternative procedure for the correction of rigid claw toe deformity.

Clawing of the digits is a deformity seen both in patients with and without rheumatoid arthritis, resulting in pain and deformity in the forefoot. After failure of conservative treatment, the Stainsby procedure is one surgical option for severe clawing and metatarsalgia in both rheumatoid and nonrheumatoid feet. Results from the originating authors (G.D. Stainsby and P.J. Briggs) are consistent and reliable; however, there is little material outside of the originating center. This article reviews our experience in the Western Sussex Hospitals NHS Trust. Sixteen consecutive patients who underwent Stainsby procedure between 2006 and 2009 were reviewed. All operations were performed by a single consultant surgeon, the senior author (S.P.). All patients were scored using the Manchester Oxford Foot and Ankle score preoperatively and postoperatively. Minimum follow-up was 6 months, with a mean follow-up of 14 months. Significant improvements in all scores were seen postoperatively. Walking scores dropped from a mean of 22 preoperatively to 12.7 postoperatively (p = 0.007). Pain scores dropped from a mean of 13.3 to 7.1 (p = 0.001). Social scores dropped from a mean 11 to 6 (p = 0.001). Overall patient satisfaction was high. The Stainsby procedure has been shown to improve function and reduce pain in patients from its originating center in both rheumatoid and nonrheumatoid feet. This study demonstrates this simple technique is reproducible and effective in reducing morbidity.