Computational studies of protein–protein dissociation by statistical potential and coarse-grained simulations: a case study on interactions between colicin E9 endonuclease and immunity proteins

Su, Zhaoqian; Wu, Yinghao

doi:10.1039/c8cp05644g

Cited by 18 publications

(13 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the physics-based potential used in our original simulation method, we further introduced a statistics-based potential that was derived from analyzing the available protein complexes in the current structural database [ 74 ]. In detail, it has the following form:

…”

Section: Model and Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein–Protein Association

Dhusia

2020

Biomolecules

Self Cite

View full text Add to dashboard Cite

The formation of functionally versatile protein complexes underlies almost every biological process. The estimation of how fast these complexes can be formed has broad implications for unravelling the mechanism of biomolecular recognition. This kinetic property is traditionally quantified by association rates, which can be measured through various experimental techniques. To complement these time-consuming and labor-intensive approaches, we developed a coarse-grained simulation approach to study the physical processes of protein–protein association. We systematically calibrated our simulation method against a large-scale benchmark set. By combining a physics-based force field with a statistically-derived potential in the simulation, we found that the association rates of more than 80% of protein complexes can be correctly predicted within one order of magnitude relative to their experimental measurements. We further showed that a mixture of force fields derived from complementary sources was able to describe the process of protein–protein association with mechanistic details. For instance, we show that association of a protein complex contains multiple steps in which proteins continuously search their local binding orientations and form non-native-like intermediates through repeated dissociation and re-association. Moreover, with an ensemble of loosely bound encounter complexes observed around their native conformation, we suggest that the transition states of protein–protein association could be highly diverse on the structural level. Our study also supports the idea in which the association of a protein complex is driven by a “funnel-like” energy landscape. In summary, these results shed light on our understanding of how protein–protein recognition is kinetically modulated, and our coarse-grained simulation approach can serve as a useful addition to the existing experimental approaches that measure protein–protein association rates.

show abstract

…”

Section: Model and Methodsmentioning

confidence: 99%

“…We further reduced the sequence redundancy from this database, which led to a final library consisting of 4960 entries of protein-protein interactions. The detailed procedure of extracting the energy parameters was described in our previous study [74].…”

Section: A Hybrid Force Field Of Intermolecular Interactions For Guidmentioning

confidence: 99%

Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein–Protein Association

Dhusia

2020

Biomolecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…In detail, Brownian dynamics algorithm was first used to drive the diffusions for all molecules in each time step of simulations by updating their Cartesian coordinates and velocities (34,35). The periodic boundary conditions are imposed.…”

Section: Methodsmentioning

confidence: 99%

Understand the Functions of Scaffold Proteins in Cell Signaling by a Mesoscopic Simulation Method

Dhusia

2020

Biophysical Journal

Self Cite

View full text Add to dashboard Cite

“…27 With the RMSF value being ≤4.0 Å, a stable molecular complex can trigger fluctuating residues that contribute to receptor response activity. 28 The results showed that the conserved region consists of Asp30 & Arg26 from peptide B5 that binds to H chain BCR with hydrogen bonds. It initiates biological responses activation with residues stable binding of Lys43 and Val114 through hydrogen bonds interaction.…”

Section: Table 2 Vaccine Properties Of B-cell Epitopementioning

confidence: 98%

Conserved B-cell epitope identification of envelope glycoprotein (GP120) HIV-1 to develop multi-strain vaccine candidate through bioinformatics approach

Kharisma

Ansori

Posa³

et al. 2021

J. Teknol. Laboratorium

View full text Add to dashboard Cite

Acquired immune deficiency syndrome (AIDS) has been identified from US patients since 1981. AIDS is caused by infection with the human immunodeficiency virus type 1 (HIV-1) which is a retrovirus. HIV-1 gp120 can be recognized by the immune system because it is located outside the virion. The conserved region is identified in gp120, and it is recognized by an immune cell which then initiates specific immune responses, viral mutation escape, and increase vaccine protection coverage, a benefit derived from the conserved region-based vaccine design. However, previous researchers have little knowledge on this conserved region as a target for vaccine design. This paper explains how the conserved region of gp120 HIV-1 is a major target for vaccine design through a bioinformatics approach. The conserved region from gp120 was explored as a vaccine design target with a bioinformatics tool that consists of B-cell epitope mapping, vaccine properties, molecular docking, and dynamic simulation. The peptide vaccine candidate of B5 with the gp120 HIV-1 conserved region was found to provoke B-cell activation through a direct pathway, produce specific antibody, and increase protection from multi-strain viral infection.

show abstract

Computational studies of protein–protein dissociation by statistical potential and coarse-grained simulations: a case study on interactions between colicin E9 endonuclease and immunity proteins

Abstract: A coarse-grained simulation method and a knowledge-based potential were developed to explore the dissociation mechanisms of protein complexes.

Cited by 18 publications

References 46 publications

Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein–Protein Association

Using Coarse-Grained Simulations to Characterize the Mechanisms of Protein–Protein Association

Understand the Functions of Scaffold Proteins in Cell Signaling by a Mesoscopic Simulation Method

Conserved B-cell epitope identification of envelope glycoprotein (GP120) HIV-1 to develop multi-strain vaccine candidate through bioinformatics approach

Contact Info

Product

Resources

About