The price and performance of commodity computer hardware and the sophistication of modern free operating systems have made it very attractive to set up computer clusters rather than purchase a multiprocessor behemoth. Clusters don't have to be dedicated rack-mounted towers of blinking lights and buzzing drives; they can also be a mixture of desktop computers that use their idle time to run jobs. There are two fundamental kinds of clusters: Beowulf-style clusters and compute farms. Beowulf clusters act as a single computer, sharing memory and CPU cycles to cooperatively solve the same problem. Compute farms don't share memory or CPU cycles and solve separate, but possibly related problems. The field of bioinformatics has algorithms that are appropriate for both kinds of clusters, but BLAST is really a job that is best suited to compute farms. There are two major reasons for this: (1) BLAST is more data-intensive than compute-intensive, and (2) large-scale BLAST searches consist of many small jobs that are easily parallelized on separate machines.
If you wish to build your own cluster, be prepared for quite a bit of work. There are plenty of considerations outside the normal window-shopping for the best price-performance ratio. For example, one of the most common problems is having sufficient power and cooling. It doesn't do much good to have a super computer that is constantly overheating and burning out its components. Total cost of ownership is a complicated equation, and you're better off not trying to solve this entirely on your own. Your best bet is to talk with people who build clusters for a living. Several companies will sell you prepackaged compute farms for running BLAST. For those who like getting their hands dirty, the bioclusters mailing list at http://bioinformatics.org has plenty of useful information in their archives and helpful members who will gladly give advice.
When designing a cluster, one of the most important decisions is where to put your BLAST databases. There are two general choices: (1) store the database on a file server and let the cluster access it remotely over a network, or (2) keep a local copy of the database on each computer. Both methods have their advantages and disadvantages, so there is no simple way to determine which is better.
It's simpler to manage the files on one computer than on multiple computers. This is particularly true if you update your BLAST databases on a frequent, perhaps daily basis. So this is one good reason to use remote databases. If you run your compute nodes diskless, it is really the only choice. The main concerns with this approach are network bandwidth and the speed of the file server. Most computers today have 100-Mbps network interfaces. This translates to 12.5 MBps. Fast computers performing insensitive searches (e.g., BLASTN) can actually exceed this transfer rate. In this case, the compute nodes will sit idle, waiting for data. But what happens when multiple computers are all connected to the same database server? Unfortunately, they must all share the same network bandwidth from the server, so if 10 compute nodes are connected to a database server, each one may get only data at 1.25 MBps. Not good. But remember that if the compute nodes have enough RAM and the databases aren't falling out of cache, subsequent searches will be very fast because they can read the database directly from memory.
One obvious improvement is to employ faster networking. Doing so increases the cost of each compute node a little and significantly increases the cost of network switches because gigabit network switches are still quite expensive. However, it is possible to use a hybrid solution in which the database server is connected to a hybrid network switch via a gigabit line and the compute nodes are connected to the switch via the more common 100-Mb interface. This is much cheaper than using gigabit everywhere, and, because exceeding 12.5 MBps is rare, it doesn't hinder performance too much.
When building file servers, people often neglect to put in enough RAM. For BLAST database servers, though, you really want as much RAM as possible. Caching applies on the file-server end, too, and if several computers request data from the file server, it's much better if it can be served from memory rather than from disk. If you're thinking of using autonomous network attached servers as a BLAST database server, think again. Most don't have gigabit networking or enough RAM.
Keeping local copies of your BLAST databases on each node of the cluster will make access to the data very fast. Most hard disks can read data at 20 to 30 MB per second or about double what you could get from common networking. If your network is slow, your cluster is large, or your searches are really insensitive, it's much better to have local copies of databases. The main concern with this approach is keeping the files synchronized and updated with respect to a master copy. This can be done via rsync or other means. However, if all the nodes update their databases at the same time across a thin pipe, this operation could take a long time, and the compute nodes may sit idle.
A lesser concern is the disks themselves. They cost money and are a potential source of hardware failure (for this reason, some people advocate running the compute nodes diskless). When discussing disks, there's a great deal of debate over IDE versus SCSI. Drives using the IDE interface are generally slower and less reliable, but are much less expensive. Experts on both sides of the debate will argue convincingly that buying one type of drive makes more sense than buying the other. However, for optimal performance, you really should access the database from cache rather than disk, and therefore the disk shouldn't really matter. Those who choose IDE or SCSI aren't necessarily fools, but people who fail to put enough RAM in their boxes are.