Investigating Intrinsically Disordered Proteins With Brownian Dynamics
Intrinsically disordered proteins (IDPs) have recently become systems of great interest due to their involvement in modulating many biological processes and their aggregation being implicated in many diseases. Since IDPs do not have a stable, folded structure, however, they cannot be easily studied...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.898838/full |
| _version_ | 1811243359734333440 |
|---|---|
| author | Surl-Hee Ahn Gary A. Huber Gary A. Huber J. Andrew McCammon J. Andrew McCammon |
| author_facet | Surl-Hee Ahn Gary A. Huber Gary A. Huber J. Andrew McCammon J. Andrew McCammon |
| author_sort | Surl-Hee Ahn |
| collection | DOAJ |
| description | Intrinsically disordered proteins (IDPs) have recently become systems of great interest due to their involvement in modulating many biological processes and their aggregation being implicated in many diseases. Since IDPs do not have a stable, folded structure, however, they cannot be easily studied with experimental techniques. Hence, conducting a computational study of these systems can be helpful and be complementary with experimental work to elucidate their mechanisms. Thus, we have implemented the coarse-grained force field for proteins (COFFDROP) in Browndye 2.0 to study IDPs using Brownian dynamics (BD) simulations, which are often used to study large-scale motions with longer time scales and diffusion-limited molecular associations. Specifically, we have checked our COFFDROP implementation with eight naturally occurring IDPs and have investigated five (Glu-Lys)25 IDP sequence variants. From measuring the hydrodynamic radii of eight naturally occurring IDPs, we found the ideal scaling factor of 0.786 for non-bonded interactions. We have also measured the entanglement indices (average Cα distances to the other chain) between two (Glu-Lys)25 IDP sequence variants, a property related to molecular association. We found that entanglement indices decrease for all possible pairs at excess salt concentration, which is consistent with long-range interactions of these IDP sequence variants getting weaker at increasing salt concentration. |
| first_indexed | 2024-04-12T14:06:04Z |
| format | Article |
| id | doaj.art-041b363eb24b47159e33d09dce0947b2 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T14:06:04Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-041b363eb24b47159e33d09dce0947b22022-12-22T03:30:04ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-06-01910.3389/fmolb.2022.898838898838Investigating Intrinsically Disordered Proteins With Brownian DynamicsSurl-Hee Ahn0Gary A. Huber1Gary A. Huber2J. Andrew McCammon3J. Andrew McCammon4Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, United StatesDepartment of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, United StatesDepartment of Pharmacology, University of California, San Diego, San Diego, CA, United StatesDepartment of Chemistry and Biochemistry, University of California, San Diego, San Diego, CA, United StatesDepartment of Pharmacology, University of California, San Diego, San Diego, CA, United StatesIntrinsically disordered proteins (IDPs) have recently become systems of great interest due to their involvement in modulating many biological processes and their aggregation being implicated in many diseases. Since IDPs do not have a stable, folded structure, however, they cannot be easily studied with experimental techniques. Hence, conducting a computational study of these systems can be helpful and be complementary with experimental work to elucidate their mechanisms. Thus, we have implemented the coarse-grained force field for proteins (COFFDROP) in Browndye 2.0 to study IDPs using Brownian dynamics (BD) simulations, which are often used to study large-scale motions with longer time scales and diffusion-limited molecular associations. Specifically, we have checked our COFFDROP implementation with eight naturally occurring IDPs and have investigated five (Glu-Lys)25 IDP sequence variants. From measuring the hydrodynamic radii of eight naturally occurring IDPs, we found the ideal scaling factor of 0.786 for non-bonded interactions. We have also measured the entanglement indices (average Cα distances to the other chain) between two (Glu-Lys)25 IDP sequence variants, a property related to molecular association. We found that entanglement indices decrease for all possible pairs at excess salt concentration, which is consistent with long-range interactions of these IDP sequence variants getting weaker at increasing salt concentration.https://www.frontiersin.org/articles/10.3389/fmolb.2022.898838/fullBrownian dynamics simulationmolecular associationsintrinsically disordered proteinsCOFFDROP force fieldBrowndye |
| spellingShingle | Surl-Hee Ahn Gary A. Huber Gary A. Huber J. Andrew McCammon J. Andrew McCammon Investigating Intrinsically Disordered Proteins With Brownian Dynamics Frontiers in Molecular Biosciences Brownian dynamics simulation molecular associations intrinsically disordered proteins COFFDROP force field Browndye |
| title | Investigating Intrinsically Disordered Proteins With Brownian Dynamics |
| title_full | Investigating Intrinsically Disordered Proteins With Brownian Dynamics |
| title_fullStr | Investigating Intrinsically Disordered Proteins With Brownian Dynamics |
| title_full_unstemmed | Investigating Intrinsically Disordered Proteins With Brownian Dynamics |
| title_short | Investigating Intrinsically Disordered Proteins With Brownian Dynamics |
| title_sort | investigating intrinsically disordered proteins with brownian dynamics |
| topic | Brownian dynamics simulation molecular associations intrinsically disordered proteins COFFDROP force field Browndye |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.898838/full |
| work_keys_str_mv | AT surlheeahn investigatingintrinsicallydisorderedproteinswithbrowniandynamics AT garyahuber investigatingintrinsicallydisorderedproteinswithbrowniandynamics AT garyahuber investigatingintrinsicallydisorderedproteinswithbrowniandynamics AT jandrewmccammon investigatingintrinsicallydisorderedproteinswithbrowniandynamics AT jandrewmccammon investigatingintrinsicallydisorderedproteinswithbrowniandynamics |