ResBoost: characterizing and predicting catalytic residues in enzymes

Abstract Background Identifying the catalytic residues in enzymes can aid in understanding the molecular basis of an enzyme's function and has significant implications for designing new drugs, identifying genetic disorders, and engineering proteins with novel functions. Since experimentally determining catalytic sites is expensive, better computational methods for identifying catalytic residues are needed. Results We propose ResBoost, a new computational method to learn characteristics of catalytic residues. The method effectively selects and combines rules of thumb into a simple, easily interpretable logical expression that can be used for prediction. We formally define the rules of thumb that are often used to narrow the list of candidate residues, including residue evolutionary conservation, 3D clustering, solvent accessibility, and hydrophilicity. ResBoost builds on two methods from machine learning, the AdaBoost algorithm and Alternating Decision Trees, and provides precise control over the inherent trade-off between sensitivity and specificity. We evaluated ResBoost using cross-validation on a dataset of 100 enzymes from the hand-curated Catalytic Site Atlas (CSA). Conclusion ResBoost achieved 85% sensitivity for a 9.8% false positive rate and 73% sensitivity for a 5.7% false positive rate. ResBoost reduces the number of false positives by up to 56% compared to the use of evolutionary conservation scoring alone. We also illustrate the ability of ResBoost to identify recently validated catalytic residues not listed in the CSA

Philadelphia Stories People and Their Places in Early America

For the average tourist, the history of Philadelphia can be like a leisurely carriage ride through Old City. The Liberty Bell. Independence Hall. Benjamin Franklin. The grooves in the cobblestone are so familiar, one barely notices the ride. Yet there are other paths to travel, and the ride can be bumpy. Beyond the famed founders, other Americans walked the streets of Philadelphia whose lives were, in their own ways, just as emblematic of the promises and perils of the new nation. Philadelphia Stories chronicles twelve of these lives to explore the city\u27s people and places from the colonial era to the years before the Civil War. This collective portrait includes men and women, Black and white Americans, immigrants and native born. If mostly forgotten today, banker Stephen Girard was one of the wealthiest men ever to have lived, and his material legacy can be seen by visiting sites such as Girard College. In a different register, but equally impressive, were the accomplishments of Sarah Thorn Tyndale. In a few short years as a widow she made enough money on her porcelain business to retire to a life as a reformer. Others faced frustration. Take, for example, Grace Growden Galloway. Born to an important family, she saw her home invaded and her property confiscated by patriot forces. Or consider the life of Francis Johnson, a Black bandleader and composer who often performed at the Musical Fund Hall, which still stands today. And yet he was barred from joining its Society. Philadelphia Stories examines their rich lives, as well as those of others who shaped the city\u27s past. Many of the places inhabited by these people survive to this day. In the pages of this book and on the streets of the city, one can visit both the people and places of Philadelphia\u27s rich history