Assessing SIRAH’s Capability to Simulate Intrinsically Disordered Proteins and Peptides

Klein, Florencia; Barrera, Exequiel; Pantano, Sergio

doi:10.1021/acs.jctc.0c00948

Cited by 20 publications

(22 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predictive capabilities of computational simulations have reached an interesting stage in the biomedical sciences. Improved simulation packages (Brooks et al, 2021;Suh et al, 2022), better force-fields (Klein et al, 2021;Souza et al, 2021;Cruz-León et al, 2021;Yungerman et al, 2022), unprecedented supercomputer power (Yamazaki et al, 2021;Kutzner et al, 2022) and creative sampling techniques (Gilabert et al, 2019;Bonati et al, 2021) have boosted the study of exceptionally complex biological problems (Mosalaganti et al, 2022;Lotz and Dickson, 2018). More studies combining theoretical approaches, computer simulations, and experiments are currently envisioning new possibilities (Sica and Smulski, 2021;Bernetti and Bussi, 2021;Miguel et al, 2021;Quevedo et al, 2019;Saen-oon et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Recently, new efforts have been made to improve computational modeling of intrinsically disordered proteins (Thomasen et al, 2022;Klein et al, 2021;Tran and Kitao, 2020). Several reviews have also been dedicated to the role of intrinsic disorder during lipid-protein interactions highlighting the effects on membrane curvature (Has, Sivadas and Das, 2022;Cornish et al, 2020;Fakhree, Blum and Claessens, 2019;Snead and Stachowiak, 2018).…”

Section: Intrinsic Disorder In Lipid-protein Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Enhanced sampling for lipid-protein interactions during membrane dynamics

Masone¹

2023

Biocell

View full text Add to dashboard Cite

The inflexible concept of membrane curvature as an independent property of lipid structures is today obsolete.Lipid bilayers behave as many-body entities with emergent properties that depend on their interactions with the environment. In particular, proteins exert crucial actions on lipid molecules that ultimately condition the collective properties of the membranes. In this review, the potential of enhanced molecular dynamics to address cell-biology problems is discussed. The cases of membrane deformation, membrane fusion, and the fusion pore are analyzed from the perspective of the dimensionality reduction by collective variables. Coupled lipid-protein interactions as fundamental determinants of large membrane remodeling events are also commented. Finally, novel strategies merging cell biology and physics are considered as future lines of research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Intrinsic Disorder In Lipid-protein Interactionsmentioning

confidence: 99%

Enhanced sampling for lipid-protein interactions during membrane dynamics

Masone¹

2023

Biocell

View full text Add to dashboard Cite

show abstract

“…In addition to an exploration of the effect of point mutations on already folded—experimental and predicted—3D structures, MD simulations are used to address the folding process, in spite of Levinthal’s paradox [ 114 , 120 , 121 , 122 ]; unfolding [ 96 , 97 , 123 ]; and dynamics of intrinsically disordered proteins (IDPs) [ 82 , 124 ]. Such tasks particularly highlight the problem of computational cost and conformational sampling in MD simulations [ 125 ].…”

Section: Determination Of Protein Stabilitymentioning

confidence: 99%

Conformational Stability and Denaturation Processes of Proteins Investigated by Electrophoresis under Extreme Conditions

Masson

Lushchekina

2022

Molecules

View full text Add to dashboard Cite

The functional structure of proteins results from marginally stable folded conformations. Reversible unfolding, irreversible denaturation, and deterioration can be caused by chemical and physical agents due to changes in the physicochemical conditions of pH, ionic strength, temperature, pressure, and electric field or due to the presence of a cosolvent that perturbs the delicate balance between stabilizing and destabilizing interactions and eventually induces chemical modifications. For most proteins, denaturation is a complex process involving transient intermediates in several reversible and eventually irreversible steps. Knowledge of protein stability and denaturation processes is mandatory for the development of enzymes as industrial catalysts, biopharmaceuticals, analytical and medical bioreagents, and safe industrial food. Electrophoresis techniques operating under extreme conditions are convenient tools for analyzing unfolding transitions, trapping transient intermediates, and gaining insight into the mechanisms of denaturation processes. Moreover, quantitative analysis of electrophoretic mobility transition curves allows the estimation of the conformational stability of proteins. These approaches include polyacrylamide gel electrophoresis and capillary zone electrophoresis under cold, heat, and hydrostatic pressure and in the presence of non-ionic denaturing agents or stabilizers such as polyols and heavy water. Lastly, after exposure to extremes of physical conditions, electrophoresis under standard conditions provides information on irreversible processes, slow conformational drifts, and slow renaturation processes. The impressive developments of enzyme technology with multiple applications in fine chemistry, biopharmaceutics, and nanomedicine prompted us to revisit the potentialities of these electrophoretic approaches. This feature review is illustrated with published and unpublished results obtained by the authors on cholinesterases and paraoxonase, two physiologically and toxicologically important enzymes.

show abstract

“…To describe fuzzy complexes, where no folding event is associated to binding, several alternative coarse-grain models are available, which were modified to be used for IDPs [49][50][51][52]. Among them we can mention AWSEM [53], PLUM [54], OPEP [55], UNRES [56], and SYRAH [57]. Analytical approaches derived from polymer physics somehow represent an ultimate stage of coarse-graining.…”

Section: Alternate Protein and Solvent Modelsmentioning

confidence: 99%

When Order Meets Disorder: Modeling and Function of the Protein Interface in Fuzzy Complexes

Sacquin-Mora

Prévost

2021

Biomolecules

View full text Add to dashboard Cite

The degree of proteins structural organization ranges from highly structured, compact folding to intrinsic disorder, where each degree of self-organization corresponds to specific functions: well-organized structural motifs in enzymes offer a proper environment for precisely positioned functional groups to participate in catalytic reactions; at the other end of the self-organization spectrum, intrinsically disordered proteins act as binding hubs via the formation of multiple, transient and often non-specific interactions. This review focusses on cases where structurally organized proteins or domains associate with highly disordered protein chains, leading to the formation of interfaces with varying degrees of fuzziness. We present a review of the computational methods developed to provide us with information on such fuzzy interfaces, and how they integrate experimental information. The discussion focusses on two specific cases, microtubules and homologous recombination nucleoprotein filaments, where a network of intrinsically disordered tails exerts regulatory function in recruiting partner macromolecules, proteins or DNA and tuning the atomic level association. Notably, we show how computational approaches such as molecular dynamics simulations can bring new knowledge to help bridging the gap between experimental analysis, that mostly concerns ensemble properties, and the behavior of individual disordered protein chains that contribute to regulation functions.

show abstract

Assessing SIRAH’s Capability to Simulate Intrinsically Disordered Proteins and Peptides

Cited by 20 publications

References 46 publications

Enhanced sampling for lipid-protein interactions during membrane dynamics

Enhanced sampling for lipid-protein interactions during membrane dynamics

Conformational Stability and Denaturation Processes of Proteins Investigated by Electrophoresis under Extreme Conditions

When Order Meets Disorder: Modeling and Function of the Protein Interface in Fuzzy Complexes

Contact Info

Product

Resources

About