TY  - JOUR
AU  - Voronin, Arthur
AU  - Weiel, Marie
AU  - Schug, Alexander
TI  - Including residual contact information into replica-exchange MD simulations significantly enriches native-like conformations
JO  - PLOS ONE
VL  - 15
IS  - 11
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - FZJ-2020-04932
SP  - e0242072 -
PY  - 2020
AB  - Proteins are complex biomolecules which perform critical tasks in living organisms. Knowledge of a protein’s structure is essential for understanding its physiological function in detail. Despite the incredible progress in experimental techniques, protein structure determination is still expensive, time-consuming, and arduous. That is why computer simulations are often used to complement or interpret experimental data. Here, we explore how in silico protein structure determination based on replica-exchange molecular dynamics (REMD) can benefit from including contact information derived from theoretical and experimental sources, such as direct coupling analysis or NMR spectroscopy. To reflect the influence from erroneous and noisy data we probe how false-positive contacts influence the simulated ensemble. Specifically, we integrate varying numbers of randomly selected native and non-native contacts and explore how such a bias can guide simulations towards the native state. We investigate the number of contacts needed for a significant enrichment of native-like conformations and show the capabilities and limitations of this method. Adhering to a threshold of approximately 75% true-positive contacts within a simulation, we obtain an ensemble with native-like conformations of high quality. We find that contact-guided REMD is capable of delivering physically reasonable models of a protein’s structure.
LB  - PUB:(DE-HGF)16
C6  - 33196676
UR  - <Go to ISI:>//WOS:000595266800006
DO  - DOI:10.1371/journal.pone.0242072
UR  - https://juser.fz-juelich.de/record/888464
ER  -