PREDICTION OF PROTEIN CONFORMATIONAL FREEDOM FROM DISTANCE CONSTRAINTS

A method is presented that generates random protein structures that fu lfil a set of upper and lower interatomic distance limits, These limit s depend on distances measured in experimental structures and the stre ngth of the interatomic interaction, Structural differences between ge nerated structures are similar to those obtained from experiment and f rom MD simulation, Although detailed aspects of dynamical mechanisms a re not covered and the extent of variations are only estimated in a re lative sense, applications to an IgG-binding domain, an SH3 binding do main, HPr, calmodulin, and lysozyme are presented which illustrate the use of the method as a fast and simple way to predict structural vari ability in proteins, The method may be used to support the design of m utants, when structural fluctuations for a large number of mutants are to be screened, The results suggest that motional freedom in proteins is ruled largely by a set of simple geometric constraints. (C) 1997 W iley-Liss, Inc.