Sampling the equilibrium kinetic network of Trp-cage in explicit solvent

Du, Weina; Bolhuis, Peter G.

doi:10.1063/1.4874299

Cited by 25 publications

(47 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Special moves for switching between stable states enable efficient sampling of all allowed path ensembles in the entire kinetic network. From these ensembles we can subsequently calculate the free energy of the system, get mechanistic insight, and calculate the entire rate network (15,20,21).…”

Section: Methodsmentioning

confidence: 99%

Rotational diffusion affects the dynamical self-assembly pathways of patchy particles

Newton

Groenewold

Kegel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Predicting the self-assembly kinetics of particles with anisotropic interactions, such as colloidal patchy particles or proteins with multiple binding sites, is important for the design of novel hightech materials, as well as for understanding biological systems, e.g., viruses or regulatory networks. Often stochastic in nature, such self-assembly processes are fundamentally governed by rotational and translational diffusion. Whereas the rotational diffusion constant of particles is usually considered to be coupled to the translational diffusion via the Stokes-Einstein relation, in the past decade it has become clear that they can be independently altered by molecular crowding agents or via external fields. Because virus capsids naturally assemble in crowded environments such as the cell cytoplasm but also in aqueous solution in vitro, it is important to investigate how varying the rotational diffusion with respect to transitional diffusion alters the kinetic pathways of self-assembly. Kinetic trapping in malformed or intermediate structures often impedes a direct simulation approach of a kinetic network by dramatically slowing down the relaxation to the designed ground state. However, using recently developed path-sampling techniques, we can sample and analyze the entire self-assembly kinetic network of simple patchy particle systems. For assembly of a designed cluster of patchy particles we find that changing the rotational diffusion does not change the equilibrium constants, but significantly affects the dynamical pathways, and enhances (suppresses) the overall relaxation process and the yield of the target structure, by avoiding (encountering) frustrated states. Besides insight, this finding provides a design principle for improved control of nanoparticle self-assembly.kinetic networks | colloids | globular proteins | transition path sampling I n nature, self-assembled complex structures and networks often provide function. Prime examples are virus capsids, where capsomer proteins with specific interaction sites self-assemble into various structures, such as icosahedrons and dodecahedrons. Protein complexes can spontaneously form in the living cell, e.g., in signal transduction networks. Self-assembly of small designed building blocks can provide novel (bio)materials with desired properties. Such building blocks can consist of proteins, synthetic polypeptides, but also of colloidal particles. Particularly, the advent of novel synthesis routes for colloidal particles with a valence, so-called "patchy particles" opened up avenues for designing colloidal superstructures. Numerous experimental, theoretical, and numerical studies have enabled understanding of the phase behavior of these particles, predicting not only interesting building blocks for new functional materials, but also demonstrating new physics (1-5). Design principles for colloidal superstructures can predict which structure is the most thermodynamically favorable state (6). However, the fact that kinetics often trumps thermodynamics can hamper such...

show abstract

Section: Methodsmentioning

confidence: 99%

Rotational diffusion affects the dynamical self-assembly pathways of patchy particles

Newton

Groenewold

Kegel

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…One way of avoiding this problem is via the path-type numbers introduced in Ref. 50. A path-type number n i IJ (λ kI ) is the number of paths in replica i joining states I and J that have crossed at maximum interface λ kI (and thus by definition also all interfaces below k), where the superscript i indicates that the paths should obey the condition of replica i in the ensemble.…”

Section: F Rate Constant Calculation For Nested Statesmentioning

confidence: 99%

“…There are several examples illustrating the applicability of RETIS on biological systems including isomerization of biological molecules 48 and protein (un)folding 49,50 (these studies employed the multiple state and single replica methodologies discussed in Secs. VI D and VI E).…”

Section: Applications Of Retismentioning

confidence: 99%

“…49 Further the (un)folding network of the Trp-cage mini-protein in explicit water resulted in a kinetic rate matrix in excellent agreement with IR experiments. 50 Saroukhani et al applied a range of methods from harmonic transition state theory (HTST) to RETIS in their study on dislocation dynamics in Al-4 wt. %Cu.…”

Section: Applications Of Retismentioning

confidence: 99%

“…14). The method has been used to sample protein folding 50 and complex formation in patchy particle systems. 88,89 …”

Section: E Single Replica Tismentioning

confidence: 99%

See 2 more Smart Citations

Foundations and latest advances in replica exchange transition interface sampling

Cabriolu

Refsnes

Bolhuis

et al. 2017

The Journal of Chemical Physics

Self Cite

View full text Add to dashboard Cite

Nearly 20 years ago, transition path sampling (TPS) emerged as an alternative method to free energy based approaches for the study of rare events such as nucleation, protein folding, chemical reactions, and phase transitions. TPS effectively performs Monte Carlo simulations with relatively short molecular dynamics trajectories, with the advantage of not having to alter the actual potential energy surface nor the underlying physical dynamics. Although the TPS approach also introduced a methodology to compute reaction rates, this approach was for a long time considered theoretically attractive, providing the exact same results as extensively long molecular dynamics simulations, but still expensive for most relevant applications. With the increase of computer power and improvements in the algorithmic methodology, quantitative path sampling is finding applications in more and more areas of research. In particular, the transition interface sampling (TIS) and the replica exchange TIS (RETIS) algorithms have, in turn, improved the efficiency of quantitative path sampling significantly, while maintaining the exact nature of the approach. Also, open-source software packages are making these methods, for which implementation is not straightforward, now available for a wider group of users. In addition, a blooming development takes place regarding both applications and algorithmic refinements. Therefore, it is timely to explore the wide panorama of the new developments in this field. This is the aim of this article, which focuses on the most efficient exact path sampling approach, RETIS, as well as its recent applications, extensions, and variations. Published by AIP Publishing.

show abstract

Computational close up on protein–protein interactions: how to unravel the invisible using molecular dynamics simulations?

Rakers

Bermudez

Keller

et al. 2015

WIREs Comput Mol Sci

View full text Add to dashboard Cite

As an essential part of many biological processes, protein-protein interactions (PPIs) offer exciting and promising opportunities for drug discovery by extension of the druggable target space. Over the last decade, studies on protein networks have significantly increased the number of identified PPIs. However, despite steadily growing data on PPIs, detailed understanding of the interaction surfaces and their dynamics remains limited. Furthermore, the development of small-molecule inhibitors of PPIs faces technological challenges, leaving the question about the 'druggability' of PPIs open. Molecular dynamics (MD) simulations may facilitate the prediction of druggable binding sites on protein-protein interfaces by detecting binding hot spots and transient pockets. MD allows for a detailed analysis of structural and functional aspects of PPIs and thus provides valuable insights into PPI mechanisms and supports the design of PPI modulators.We provide an overview on the main areas of MD applications to PPIs including structural investigations and the design of PPI disruptors. Emphasizing the beneficial synergies between computational and experimental techniques, MD techniques are also frequently applied to low-resolution structural data and have been used to elucidate structure and movements of complex macromolecular structures relevant for biological processes.

show abstract

Sampling the equilibrium kinetic network of Trp-cage in explicit solvent

Cited by 25 publications

References 58 publications

Rotational diffusion affects the dynamical self-assembly pathways of patchy particles

Rotational diffusion affects the dynamical self-assembly pathways of patchy particles

Foundations and latest advances in replica exchange transition interface sampling

Computational close up on protein–protein interactions: how to unravel the invisible using molecular dynamics simulations?

Contact Info

Product

Resources

About