The unfolded state of proteins presents many challenges to elucidate the structural basis for biological function. This state is characterized by a large degree of structural heterogeneity which makes it difficult to generate structural models. However, recent experiments into the initial folding events of the 104-residue ribonuclease homologue onconase (ONC) were able to identify the regions in the protein that participate in the initial folding of this protein. Therefore, to gain additional structural insight into the unfolded state of proteins, this study utilized molecular dynamics simulations using the UNited-RESidue (UNRES) force field to evaluate whether there is a good agreement between the experimentally determined initial structures and the structures identified by computer simulations along a folding pathway. Indeed, these UNRES simulations accurately identified the two regions experimentally observed to form the initial native structure along the folding pathway of ONC. In addition, these regions are determined to be chain folding initiation sites (CFIS) according to methods developed previously. Subsequent self-organization maps (SOM) analysis has revealed key structural states involved in these early folding events.

Hendrix, E., Motta, S., Gahl, R., He, Y. (2022). Insight into the Initial Stages of the Folding Process in Onconase Revealed by UNRES. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 126(40), 7934-7942 [10.1021/acs.jpcb.2c04770].

Insight into the Initial Stages of the Folding Process in Onconase Revealed by UNRES

Motta, Stefano
Secondo
;
2022

Abstract

The unfolded state of proteins presents many challenges to elucidate the structural basis for biological function. This state is characterized by a large degree of structural heterogeneity which makes it difficult to generate structural models. However, recent experiments into the initial folding events of the 104-residue ribonuclease homologue onconase (ONC) were able to identify the regions in the protein that participate in the initial folding of this protein. Therefore, to gain additional structural insight into the unfolded state of proteins, this study utilized molecular dynamics simulations using the UNited-RESidue (UNRES) force field to evaluate whether there is a good agreement between the experimentally determined initial structures and the structures identified by computer simulations along a folding pathway. Indeed, these UNRES simulations accurately identified the two regions experimentally observed to form the initial native structure along the folding pathway of ONC. In addition, these regions are determined to be chain folding initiation sites (CFIS) according to methods developed previously. Subsequent self-organization maps (SOM) analysis has revealed key structural states involved in these early folding events.
Articolo in rivista - Articolo scientifico
Onconase; UNRES; Self Organizing Maps; Molecular Dynamics
English
30-set-2022
2022
126
40
7934
7942
none
Hendrix, E., Motta, S., Gahl, R., He, Y. (2022). Insight into the Initial Stages of the Folding Process in Onconase Revealed by UNRES. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 126(40), 7934-7942 [10.1021/acs.jpcb.2c04770].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/420659
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