user: How many NBA basketball teams are in California?

assistant: There are 4 NBA basketball teams in California: Golden State Warriors, Los Angeles Lakers, Los Angeles Clippers, and Sacramento Kings.

user: What is the best location for a family vacation in western Europe?

assistant: The best location depends on individual tastes and preferences.  

For a vacation in a city, you can’t beat Paris.  There is a large range of available cuisine, from inexpensive bistros and cafes, to very expensive, Michelin starred restaurants.  It is hard to get a bad meal in Paris.  The sightseeing also is impressive, with modern architecture combined with classic structures, and many museums to fill your days. Getting around Paris is very easy, as it is a very walkable city and also has an efficient and relatively inexpensive public transportation system.  

For a lake vacation, Lake Como is wonderful, and in particular Bellagio, which is widely regarded as the prettiest village in Lake Como.  Getting to Bellagio is fairly easy, as it’s close to Milan.  The food is reasonably priced, although it’s generally northern Italian food (with limited options for other ethnic food).  Transportation around the lake is convenient with an efficient ferry service on Lake Como, although getting into the individual villages can be a bit challenging given the hills (so expect to walk!).  Many villages near Bellagio are also very quaint, and within walking distance – you’ll definitely get good exercise going from village to village.

For a seaside vacation, Dubrovnik is a great choice.  It’s not so convenient to get there from the United States, especially for those in the western United States since there are no direct flights.  However, it’s well worth the trip.  This walled city is jaw dropping beautiful.  The people are among the friendliest in Europe.  The food is fairly inexpensive and delicious, with a lot of seafood options.  And some restaurants are literally perched off of a cliff, so the views are incredible. Croatian dried lemons and oranges are fantastic, and a specialty of the region.  There also is beautiful pottery.

user: What is the nuclear magnetic resonance spectroscopy of proteins?

assistant: Nuclear magnetic resonance spectroscopy of proteins (usually abbreviated protein NMR) is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

NMR involves the quantum-mechanical properties of the central core ("nucleus") of the atom. These properties depend on the local molecular environment, and their measurement provides a map of how the atoms are linked chemically, how close they are in space, and how rapidly they move with respect to each other. These properties are fundamentally the same as those used in the more familiar magnetic resonance imaging (MRI), but the molecular applications use a somewhat different approach, appropriate to the change of scale from millimeters (of interest to radiologists) to nanometers (bonded atoms are typically a fraction of a nanometer apart), a factor of a million. This change of scale requires much higher sensitivity of detection and stability for long term measurement. In contrast to MRI, structural biology studies do not directly generate an image, but rely on complex computer calculations to generate three-dimensional molecular models.

Currently most samples are examined in a solution in water, but methods are being developed to also work with solid samples. Data collection relies on placing the sample inside a powerful magnet, sending radio frequency signals through the sample, and measuring the absorption of those signals. Depending on the environment of atoms within the protein, the nuclei of individual atoms will absorb different frequencies of radio signals. Furthermore, the absorption signals of different nuclei may be perturbed by adjacent nuclei. This information can be used to determine the distance between nuclei. These distances in turn can be used to determine the overall structure of the protein.

A typical study might involve how two proteins interact with each other, possibly with a view to developing small molecules that can be used to probe the normal biology of the interaction ("chemical biology") or to provide possible leads for pharmaceutical use (drug development). Frequently, the interacting pair of proteins may have been identified by studies of human genetics, indicating the interaction can be disrupted by unfavorable mutations, or they may play a key role in the normal biology of a "model" organism like the fruit fly, yeast, the worm C. elegans, or mice. To prepare a sample, methods of molecular biology are typically used to make quantities by bacterial fermentation. This also permits changing the isotopic composition of the molecule, which is desirable because the isotopes behave differently and provide methods for identifying overlapping NMR signals.