Rotamer Libraries

Libraries

Rotamer libraries can be backbone-independent or depend on the backbone conformation of the secondary structure (this was discussed in Dunbrack 2002). Table 13.1 lists the published rotamer libraries. The original motivation for using a rotamer library was to make the side-chain conformational space as small as possible in order to reduce computer memory requirements. Because 3D structural data were limited, the initial rotamer libraries were created without considering backbone conformation. The first rotamer library (Ponder and Richards 1987) was useful when discriminating sequences that are compatible with the known backbone conformation in the protein core. This led to a number of independent groups to successfully design the protein core de novo (Desjarlais and Handel 1995; Harbury et al. 1995; Dahiyat and Mayo 1997; Kono et al. 1998; Desjarlais and Handel 1999).

However, the desire to accurately model the side chains has resulted in significantly larger rotamer libraries in recent years. In particular, as more structures were determined, it became clear that the backbone and side-chain conformations were correlated. This led to the creation of the first backbone-dependent rotamer library that reflects the principles of structural chemistry (Dunbrack and Karplus 1993). Also, with more structures to choose from, one could impose stricter criteria when selecting data to create libraries. At the present, most of the libraries are created using only high-resolution crystal structures (2.0 A or better). In addition, Lovell and coworkers (Lovell et al. 2000) further eliminated the side chains with high B-factors (B factor of < 40A2 was recommended), steric clashes, or ambiguous amide or his-tidine ring orientations. They also used the peak values of fitted Gaussian functions rather than the means to avoid strained conformations due to skewed angle distributions. Among the available rotamer libraries today, the most widely used are the backbone-dependent library developed by Dunbrack and coworkers (Dunbrack and Cohen 1997) and the backbone-independent library developed by Lovell and coworkers (Lovell et al. 2000), both of which can be downloaded from the Web.* Other rotamer libraries derived from these original libraries are also available.

* http://dunbrack.fccc.edu/bbdep/bbdepformat.php and http://kinemage.biochem.duke.edu/databases/ rotamer.php, respectively.

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