pKD: re-designing protein pK(a) values

The pK(a) values in proteins govern the pH-dependence of protein stability and enzymatic activity. A large number of mutagenesis experiments have been carried out in the last three decades to re-engineer the pH-activity and pH-stability profile of enzymes and proteins. We have developed the pKD webserver (), which predicts sets of point mutations that will change the pK(a) values of a set of target residues in a given direction, thus allowing for targeted re-design of the pH-dependent characteristics of proteins. The server provides the user with an interactive experience for re-designing pK(a) values by pre-calculating ΔpK(a) values from all feasible point mutations. Design solutions are found in less than 10 min for a typical design job for a medium-sized protein. Mutant ΔpK(a) values calculated by the pKD web server are in close agreement with those produced by comparing results from full-fledged pK(a) calculation methods

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead