Replica Exchange Molecular Dynamics: A Practical Application Protocol with Solutions to Common Problems and a Peptide Aggregation and Self-Assembly Example

Qi, Ruxi; Wei, Guanghong; Ma, Buyong; Nussinov, Ruth

doi:10.1007/978-1-4939-7811-3_5

Cited by 84 publications

(86 citation statements)

References 33 publications

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“…The ionized hydroxyl group has stronger affinity to water than the neutral, thus, complete covering is less typical of it in non-ionic micelles, too. So that, the application of advanced sampling techniques like replica exchange MD [12] may be strongly needed for these systems despite their relative simplicity.…”

Section: Resultsmentioning

confidence: 99%

Molecular dynamics study of an acid-base indicator dye in Triton X-100 non-ionic micelles

Farafonov¹,

Lebed²,

Khimenko³

et al. 2020

VKhKhT

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Despite wide laboratory and industrial use, the structure of non-ionic surfactant micelles and the state of molecular probes adsorbed by them are relatively poorly studied by computational methods in comparison to the ionic surfactants. The state of an acid-base indicator dye, namely, 2,6-dinitro-4-n-dodecylphenol, solubilized by micelles of Triton X-100 non-ionic surfactant, was revealed by means of molecular dynamics simulations. Both neutral and ionized protolytic forms were considered. The average positioning of the forms with respect to micelle, composition of their local environment and number of hydrogen bonds with water molecules were obtained and compared with those in ionic micelles. The dye was found to be located on the surface of hydrocarbon core and be significantly less hydrated than in ionic micelles due to covering by polyoxyethylene chains. Both forms are localized similarly, while the anionic form is hydrated stronger than the neutral one, which resembles the situation in ionic micelles. The convergence of simulation results in such micelles is found to be slower than in the ionic micelles, especially for the neutral form.

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Section: Resultsmentioning

confidence: 99%

Molecular dynamics study of an acid-base indicator dye in Triton X-100 non-ionic micelles

Farafonov¹,

Lebed²,

Khimenko³

et al. 2020

VKhKhT

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“…In order to both explore and adequately sample conformation space, a two phase procedure was used. In the first phase, temperature replica-exchange molecular dynamics (tREMD) 36,37 was used to encourage the complex to explore new conformations. The second phase used equilibrium molecular dynamics simulations to thoroughly sample the conformation space explored by tREMD.…”

Section: Methodsmentioning

confidence: 99%

Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2

Nelson

Buzko

Bassett³

et al. 2020

Preprint

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The Receptor Binding Domain (RBD) of the SARS-CoV-2 surface spike (S) protein interacts with host angiotensin converting enzyme 2 (ACE2) to gain entry to host cells and initiate infection1–3. Detailed, accurate understanding of key interactions between S RBD and ACE2 provides critical information that may be leveraged in the development of strategies for the prevention and treatment of COVID-19. Utilizing the published sequences and cryo-EM structures of both the viral S RBD and ACE24,5, we performed in silico molecular dynamics (MD) simulations of free S RBD and of its interaction with ACE2 over the exceptionally long durations of 2.9 and 2 milliseconds, respectively, to elucidate the nature and relative affinity of S RBD surface residues for the ACE2 binding region. Our findings reveal that free S RBD has assumed an optimized ACE2 binding-ready conformation, incurring little entropic penalty for binding, an evolutionary adaptation that contributes to its high affinity for the receptor6. We further identified high probability molecular binding interactions that inform both vaccine design and therapeutic development, which may include recombinant ACE2-based spike decoys7 and/or allosteric S RBD-ACE2 binding inhibitors8,9 to prevent or arrest infection and thus disease.

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“…Of these methods, T emperature r eplica e xchange MD (T-REMD, parallel tempering), which combines MD and MC [ 86 ], deserves explanation, as it forms the basis for a wide range of methods. Multiple independent MD simulations are run in parallel across a ladder of different temperatures ( Figure 2a ).…”

Section: Enhanced Sampling Algorithmsmentioning

confidence: 99%

Computational methods for exploring protein conformations

Allison

2020

Biochemical Society Transactions

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Proteins are dynamic molecules that can transition between a potentially wide range of structures comprising their conformational ensemble. The nature of these conformations and their relative probabilities are described by a high-dimensional free energy landscape. While computer simulation techniques such as molecular dynamics simulations allow characterisation of the metastable conformational states and the transitions between them, and thus free energy landscapes, to be characterised, the barriers between states can be high, precluding efficient sampling without substantial computational resources. Over the past decades, a dizzying array of methods have emerged for enhancing conformational sampling, and for projecting the free energy landscape onto a reduced set of dimensions that allow conformational states to be distinguished, known as collective variables (CVs), along which sampling may be directed. Here, a brief description of what biomolecular simulation entails is followed by a more detailed exposition of the nature of CVs and methods for determining these, and, lastly, an overview of the myriad different approaches for enhancing conformational sampling, most of which rely upon CVs, including new advances in both CV determination and conformational sampling due to machine learning.

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Replica Exchange Molecular Dynamics: A Practical Application Protocol with Solutions to Common Problems and a Peptide Aggregation and Self-Assembly Example

Cited by 84 publications

References 33 publications

Molecular dynamics study of an acid-base indicator dye in Triton X-100 non-ionic micelles

Molecular dynamics study of an acid-base indicator dye in Triton X-100 non-ionic micelles

Millisecond-scale molecular dynamics simulation of spike RBD structure reveals evolutionary adaption of SARS-CoV-2 to stably bind ACE2

Computational methods for exploring protein conformations

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