TY - JOUR
AU - Welsh, William J.
AB - We have previously demonstrated that calculation of contact‐dependent secondary structure propensity (CSSP) is highly sensitive in detecting non‐native β‐strand propensities in the core sequences of known amyloidogenic proteins. Here we describe a CSSP method based on an artificial neural network that rapidly and accurately quantifies the influence of tertiary contacts (TCs) on secondary structure propensity in local regions of protein sequences. The present method exhibited 72% accuracy in predicting the alternate secondary structure adopted by chameleon sequences located in highly disparate TC regions. Analysis of 1930 nonhomologous protein domains reveals that the α‐helix and the β‐strand largely share the same sequence context, and that tertiary context is a major determinant of the native conformation. Conversely, it appears that the propensity of random coils for either the α‐helix or the β‐strand is largely invariant to tertiary effects. The present CSSP method successfully reproduced the amyloidogenic character observed in local regions of the human islet amyloid polypeptide (hIAPP). Furthermore, CSSP profiles were strongly correlated (r = 0.76) with the observed mutational effects on the aggregation rate of acylphosphatase. Taken together, these results provide compelling evidence in support of the present CSSP approach as a sensitive probe useful for analysis of full‐length proteins and for detection of core sequences that may trigger amyloid fibril formation. The combined speed and simplicity of the CSSP method lends itself to proteome‐wide analysis of the amyloidogenic nature of common proteins. Proteins 2005. © 2005 Wiley‐Liss, Inc.
TI - Rapid assessment of contact‐dependent secondary structure propensity: Relevance to amyloidogenic sequences
JF - Proteins: Structure Function and Bioinformatics
DO - 10.1002/prot.20477
DA - 2005-01-01
UR - https://www.deepdyve.com/lp/wiley/rapid-assessment-of-contact-dependent-secondary-structure-propensity-YWlPsHuh0b
SP - 110
EP - 117
VL - 60
IS - 1
DP - DeepDyve
ER -