Naslov
Conformational averaging in structural biology : issues, challenges and computational solutions

Autori
Kruschel, Daniela ; Žagrović, Bojan

Izvornik
Molecular biosystems (1742-206X) 5 (2009), 12; 1606-1616

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
molecular dynamics; molecular-dynamics simulation; macromolecular structure determination; coupling-constant restraints; protein-protein interactions; residual dipolar couplings; Nmr order parameters; acyl carrier protein; torsion angles; structure refinement; distance restraints

Sažetak
Most experimental methods in structural biology provide time-and ensemble-averaged signals and, consequently, molecular structures based on such signals often exhibit only idealized, average features. Second, most experimental signals are only indirectly related to real, molecular geometries, and solving a structure typically involves a complicated procedure, which may not always result in a unique solution. To what extent do such conformationally-averaged, non-linear experimental signals and structural models derived from them accurately represent the underlying microscopic reality? Are there some structural motifs that are actually artificially more likely to be "seen" in an experiment simply due to the averaging artifact? Finally, what are the practical consequences of ignoring the averaging effects when it comes to functional and mechanistic implications that we try to glean from experimentally-based structural models? In this review, we critically address the work that has been aimed at studying such questions. We summarize the details of experimental methods typically used in structural biology (most notably nuclear magnetic resonance, X-ray crystallography and different types of spectroscopy), discuss their individual susceptibility to conformational (motional) averaging, and review several theoretical approaches, most importantly molecular dynamics simulations that are increasingly being used to aid experimentalists in interpreting structural biology experiments.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Biologija

POVEZANOST RADA